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Luo Z, Lv L. Impacts of CD36 Variants on Plasma Lipid Levels and the Risk of Early-Onset Coronary Artery Disease: A Systematic Review and Meta-Analysis. Cardiovasc Ther 2025; 2025:8098173. [PMID: 40040886 PMCID: PMC11879577 DOI: 10.1155/cdr/8098173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 01/30/2025] [Indexed: 03/06/2025] Open
Abstract
Background: Recent studies have indicated that cluster of differentiation 36 (CD36) is closely linked to dyslipidemia and early-onset coronary artery disease (EOCAD). This study is aimed at investigating the impacts of CD36 gene variants on lipid profiles and EOCAD risk. Methods: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until June 15, 2024. Results: In total, 25 studies (11,494 individuals) were included for the analysis. The A allele carriers of the rs1761667 variant had higher high-density lipoprotein cholesterol (HDL-C) levels and higher EOCAD risk than noncarriers. In contrast, the G allele carriers of the rs1049673 and rs3211956 variants had lower low-density lipoprotein cholesterol (LDL-C) levels and lower EOCAD risk than noncarriers. Subgroup analysis indicated that the antiatherosclerotic impact and reduced EOCAD risk were primarily observed in Chinese with rs1049673 and rs3211956. Conclusions: The rs1761667, rs1049673, and rs3211956 variants of the CD36 gene have significant impacts on lipid levels and may serve as genetic markers for the risk of EOCAD primarily in Chinese. The impacts of CD36 variants on EOCAD risk are mediated, at least partly, by dyslipidemia. Genetic screening of CD36 gene variants may be helpful for early intervention or prevention of EOCAD in individuals with high risk factors.
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Affiliation(s)
- Zhi Luo
- Department of Cardiology, Suining Central Hospital, Suining, Sichuan, China
| | - Lingwei Lv
- Department of Orthopedics, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
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2
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Roca-Rivada A, Do Cruzeiro M, Denis RG, Zhang Q, Rouault C, Rouillé Y, Launay JM, Cruciani-Guglielmacci C, Mattot V, Clément K, Jockers R, Dam J. Whole-body deletion of Endospanin 1 protects from obesity-associated deleterious metabolic alterations. JCI Insight 2024; 9:e168418. [PMID: 38716728 PMCID: PMC11141941 DOI: 10.1172/jci.insight.168418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/27/2024] [Indexed: 05/12/2024] Open
Abstract
The importance of the proper localization of most receptors at the cell surface is often underestimated, although this feature is essential for optimal receptor response. Endospanin 1 (Endo1) (also known as OBRGRP or LEPROT) is a protein generated from the same gene as the human leptin receptor and regulates the trafficking of proteins to the surface, including the leptin receptor. The systemic role of Endo1 on whole-body metabolism has not been studied so far. Here, we report that general Endo1-KO mice fed a high-fat diet develop metabolically healthy obesity with lipid repartitioning in organs and preferential accumulation of fat in adipose tissue, limited systematic inflammation, and better controlled glucose homeostasis. Mechanistically, Endo1 interacts with the lipid translocase CD36, thus regulating its surface abundance and lipid uptake in adipocytes. In humans, the level of Endo1 transcripts is increased in the adipose tissue of patients with obesity, but low levels rather correlate with a profile of metabolically healthy obesity. We suggest here that Endo1, most likely by controlling CD36 cell surface abundance and lipid uptake in adipocytes, dissociates obesity from diabetes and that its absence participates in metabolically healthy obesity.
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Affiliation(s)
- Arturo Roca-Rivada
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Marcio Do Cruzeiro
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Raphaël G.P. Denis
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
- Unité de Biologie Fonctionnelle et Adaptative, Université Paris Cité, CNRS, 75013 Paris, France
| | - Qiang Zhang
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Christine Rouault
- Sorbonne Université, Inserm, Nutrition and obesities: systemic approaches, Nutriomics, Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique Hopitaux de Paris, Paris, France
| | - Yves Rouillé
- Université de Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France
| | | | | | - Virginie Mattot
- Université Paris Cité, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, F-59000, Lille, France
| | - Karine Clément
- Sorbonne Université, Inserm, Nutrition and obesities: systemic approaches, Nutriomics, Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique Hopitaux de Paris, Paris, France
| | - Ralf Jockers
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
| | - Julie Dam
- Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France
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Glatz JFC, Heather LC, Luiken JJFP. CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease. Physiol Rev 2024; 104:727-764. [PMID: 37882731 DOI: 10.1152/physrev.00011.2023] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 10/02/2023] [Accepted: 10/22/2023] [Indexed: 10/27/2023] Open
Abstract
The multifunctional membrane glycoprotein CD36 is expressed in different types of cells and plays a key regulatory role in cellular lipid metabolism, especially in cardiac muscle. CD36 facilitates the cellular uptake of long-chain fatty acids, mediates lipid signaling, and regulates storage and oxidation of lipids in various tissues with active lipid metabolism. CD36 deficiency leads to marked impairments in peripheral lipid metabolism, which consequently impact on the cellular utilization of multiple different fuels because of the integrated nature of metabolism. The functional presence of CD36 at the plasma membrane is regulated by its reversible subcellular recycling from and to endosomes and is under the control of mechanical, hormonal, and nutritional factors. Aberrations in this dynamic role of CD36 are causally associated with various metabolic diseases, in particular insulin resistance, diabetic cardiomyopathy, and cardiac hypertrophy. Recent research in cardiac muscle has disclosed the endosomal proton pump vacuolar-type H+-ATPase (v-ATPase) as a key enzyme regulating subcellular CD36 recycling and being the site of interaction between various substrates to determine cellular substrate preference. In addition, evidence is accumulating that interventions targeting CD36 directly or modulating its subcellular recycling are effective for the treatment of metabolic diseases. In conclusion, subcellular CD36 localization is the major adaptive regulator of cellular uptake and metabolism of long-chain fatty acids and appears a suitable target for metabolic modulation therapy to mend failing hearts.
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Affiliation(s)
- Jan F C Glatz
- Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
- Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Lisa C Heather
- Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom
| | - Joost J F P Luiken
- Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
- Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands
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El Ouali EM, Kartibou J, Del Coso J, El Makhzen B, Bouguenouch L, El Harane S, Taib B, Weiss K, Knechtle B, Mesfioui A, Zouhal H. Genotypic and Allelic Distribution of the CD36 rs1761667 Polymorphism in High-Level Moroccan Athletes: A Pilot Study. Genes (Basel) 2024; 15:419. [PMID: 38674354 PMCID: PMC11049038 DOI: 10.3390/genes15040419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/22/2024] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
Previous studies have shown that variations in the CD36 gene may affect phenotypes associated with fat metabolism as the CD36 protein facilitates the transport of fatty acids to the mitochondria for oxidation. However, no previous study has tested whether variations in the CD36 gene are associated with sports performance. We investigated the genotypic and allelic distribution of the single-nucleotide polymorphism (SNP) rs1761667 in the CD36 gene in elite Moroccan athletes (cyclists and hockey players) in comparison with healthy non-athletes of the same ethnic origin. Forty-three Moroccan elite male athletes (nineteen cyclists and twenty-four field hockey players) belonging to the national teams of their respective sports (athlete group) were compared to twenty-eight healthy, active, male university students (control group). Genotyping of the CD36 rs1761667 (G>A) SNP was performed via polymerase chain reaction (PCR) and Sanger sequencing. A chi-square (χ2) test was used to assess the Hardy-Weinberg equilibrium (HWE) and to compare allele and genotype frequencies in the "athlete" and "control" groups. The genotypic distribution of the CD36 rs1761667 polymorphism was similar in elite athletes (AA: 23.81, AG: 59.52, and GG: 16.67%) and controls (AA: 19.23, AG: 69.23, and GG: 11.54%; χ2 = 0.67, p = 0.71). However, the genotypic distribution of the CD36 rs1761667 polymorphism was different between cyclists (AA: 0.00, AG: 72.22, and GG: 27.78%) and hockey players (AA: 41.67, AG: 50.00, and GG: 8.33%; χ2 = 10.69, p = 0.004). Specifically, the frequency of the AA genotype was significantly lower in cyclists than in hockey players (p = 0.02). In terms of allele frequency, a significant difference was found between cyclists versus field hockey players (χ2 = 7.72, p = 0.005). Additionally, there was a predominance of the recessive model in cyclists over field hockey players (OR: 0.00, 95% CI: 0.00-0.35, p = 0.002). Our study shows a significant difference between cyclists and field hockey players in terms of the genotypic and allelic frequency of the SNP rs1761667 of the CD36 gene. This divergence suggests a probable association between genetic variations in the CD36 gene and the type of sport in elite Moroccan athletes.
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Affiliation(s)
- El Mokhtar El Ouali
- Laboratory of Biology and Health, Department of Biology, Ibn Tofail University, Kenitra 14000, Morocco; (E.M.E.O.); (J.K.); (A.M.)
| | - Jihan Kartibou
- Laboratory of Biology and Health, Department of Biology, Ibn Tofail University, Kenitra 14000, Morocco; (E.M.E.O.); (J.K.); (A.M.)
| | - Juan Del Coso
- Sport Sciences Research Centre, Rey Juan Carlos University, 28943 Fuenlabrada, Spain
| | - Badreddine El Makhzen
- Medical Genetics Unit, Central Laboratory, CHU Hassan II, Faculty of Medicine, Pharmacy and Dentistry, Sidi Mohamed Ben Abdellah University, Fez 30040, Morocco; (B.E.M.); (L.B.)
| | - Laila Bouguenouch
- Medical Genetics Unit, Central Laboratory, CHU Hassan II, Faculty of Medicine, Pharmacy and Dentistry, Sidi Mohamed Ben Abdellah University, Fez 30040, Morocco; (B.E.M.); (L.B.)
| | - Sanae El Harane
- Institute of Sports Professions, Ibn Tofail University, Kenitra 14000, Morocco;
| | - Bouchra Taib
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland;
| | - Katja Weiss
- Institute of Primary Care, University of Zurich, 8032 Zurich, Switzerland; (K.W.); (B.K.)
| | - Beat Knechtle
- Institute of Primary Care, University of Zurich, 8032 Zurich, Switzerland; (K.W.); (B.K.)
- Medbase St. Gallen Am Vadianplatz, 9000 St. Gallen, Switzerland
| | - Abdelhalem Mesfioui
- Laboratory of Biology and Health, Department of Biology, Ibn Tofail University, Kenitra 14000, Morocco; (E.M.E.O.); (J.K.); (A.M.)
| | - Hassane Zouhal
- M2S (Laboratoire Mouvement, Sport et Santé)—EA 1274, University of Rennes, 35000 Rennes, France
- Institut International des Sciences du Sport (2I2S), 35850 Irodouër, France
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Enciso Ramírez MA, Reyes Castillo Z, Valdés Miramontes EH. [Genetic variants in CD36: emerging role in oral fat perception and food preferences]. NUTR HOSP 2023; 40:1262-1269. [PMID: 37705436 DOI: 10.20960/nh.04711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Abstract
Introduction CD36 is a receptor involved in physiologic, metabolic and pathologic processes. Due to its affinity for long-chain fatty acids, it has been postulated as a taste receptor of fatty taste. In this review, the emerging genetic evidence linking CD36 to oral fat perception is analyzed. A systematic literature search was conducted in PubMed, published articles from 2000 to 2022 were considered. Multiple studies have shown an association of some genetic variants in CD36 with fat foods preferences and it has been suggested that these variants can modify oral fat perception thresholds however the evidence is still heterogeneous; this can be explained by the genetic diversity of populations, the nutritional status and participant's characteristics, as well as other methodological aspects. Other factors involved in oral fat perception were and identified and discussed including the interaction with other flavors, hormones, and epigenetic factors. The conclusion is that the evidence supporting the role of CD36 as a dietary lipid receptor, the role of its genetic variants in fat acids oral perception thresholds and food preferences is intermediate level and more investigations are necessary in other populations with large number of participants as well as considering the interaction between different hormones and the expression of CD36.
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Affiliation(s)
| | - Zyanya Reyes Castillo
- Laboratorio de Biomedicina y Biotecnología para la Salud. Centro Universitario del Sur. Universidad de Guadalajara. Instituto de Investigaciones en Comportamiento Alimentario y Nutrición. Universidad de Guadalajara
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Yazdanpanah Z, Salehi-Abargouei A, Mollahosseini M, Sheikhha MH, Mirzaei M, Mozaffari-Khosravi H. The cluster of differentiation 36 ( CD36) rs1761667 polymorphism interacts with dietary patterns to affect cardiometabolic risk factors and metabolic syndrome risk in apparently healthy individuals. Br J Nutr 2023; 130:1510-1520. [PMID: 36927543 DOI: 10.1017/s0007114523000570] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Several studies have examined the association between CD36 rs1761667 polymorphism with cardiometabolic risk factors and metabolic syndrome (MetS). This study aimed to investigate the interactions between rs1761667 polymorphism and dietary patterns on the cardiometabolic risk factors and the risk of MetS in apparently healthy individuals aged 20-70 years. Food consumption data were acquired using a validated semi-quantitative FFQ. Dietary patterns were identified by factor analysis. CD36 rs1761667 was genotyped by PCR-restriction fragment length polymorphism. The gene-diet interaction was detected by the general linear model or logistic regression. Significant or marginally significant interactions were observed between healthy dietary pattern (HDP) and CD36 rs1761667 on weight (P = 0·006), BMI (P = 0·009), waist circumference (P = 0·005), hip circumference (P = 0·06), body muscle percentage (P = 0·02), body fat percentage (P = 0·09), TAG-glucose index (P = 0·057), atherogenic index of plasma (P = 0·07), the risk of MetS (P = 0·02), risk of abdominal obesity (P = 0·02) and elevated blood pressure (P = 0·07). Besides, a gene-diet interaction was detected between the traditional dietary pattern and rs1761667 variants on odds of hypertriglyceridaemia (P = 0·02). The adherence to HDP was associated with a lower weight, BMI and higher odds of HDL-cholesterol only in A-allele carriers. In conclusion, adherence to HDP (a diet with high fibre, fish and dairy products) can be more effective on some cardiometabolic risk factors and risk of MetS components in the A-allele carrier than the GG genotype of rs1761667 polymorphism. However, future studies are required to shed light on this issue.
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Affiliation(s)
- Zeinab Yazdanpanah
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Yazd Cardiovascular Research Centre, Non-communicable Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mehdi Mollahosseini
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Hasan Sheikhha
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Mirzaei
- Yazd Cardiovascular Research Centre, Non-communicable Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Bartoszewicz M, Rać M. Prognostic Value of the Selected Polymorphisms in the CD36 Gene in the Domain-Encoding Lipid-Binding Region at a 10-Year Follow-Up for Early-Onset CAD Patients. Biomedicines 2023; 11:biomedicines11051332. [PMID: 37239003 DOI: 10.3390/biomedicines11051332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/23/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
The polymorphism of the CD36 gene may have a decisive impact on the formation and progression of atherosclerotic changes. The aim of the study was to confirm the prognostic values of the previously studied polymorphisms in the CD36 gene within a 10-year follow-up period. This is the first published report confirming the long-term observation of patients with CAD. The study group covered 100 early-onset CAD patients. It included 26 women not older than 55 years and 74 men not older than 50 years, tested in a ten-year study as a long-term follow-up after the first cardiovascular episode. There are no notable differences between the CD36 variants and the number of fatalities during observation, fatalities due to cardiological reasons, cases of myocardial infarction within a ten-year observation period, hospitalizations for cardiovascular issues, all cardiovascular occurrences, and the number of months lived. We have shown that the CD36 variants analyzed in this study do not appear to be related to the risk of early CAD occurrence in the Caucasian population in long-term observation.
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Affiliation(s)
- Michał Bartoszewicz
- Psychosocial and Medical Rehabilitation Centre, West Pomeranian Centre Oncology, 71-730 Szczecin, Poland
| | - Monika Rać
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-204 Szczecin, Poland
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Samovski D, Jacome-Sosa M, Abumrad NA. Fatty Acid Transport and Signaling: Mechanisms and Physiological Implications. Annu Rev Physiol 2023; 85:317-337. [PMID: 36347219 DOI: 10.1146/annurev-physiol-032122-030352] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Long-chain fatty acids (FAs) are components of plasma membranes and an efficient fuel source and also serve as metabolic regulators through FA signaling mediated by membrane FA receptors. Impaired tissue FA uptake has been linked to major complications of obesity, including insulin resistance, cardiovascular disease, and type 2 diabetes. Fatty acid interactions with a membrane receptor and the initiation of signaling can modify pathways related to nutrient uptake and processing, cell proliferation or differentiation, and secretion of bioactive factors. Here, we review the major membrane receptors involved in FA uptake and FA signaling. We focus on two types of membrane receptors for long-chain FAs: CD36 and the G protein-coupled FA receptors FFAR1 and FFAR4. We describe key signaling pathways and metabolic outcomes for CD36, FFAR1, and FFAR4 and highlight the parallels that provide insight into FA regulation of cell function.
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Affiliation(s)
- Dmitri Samovski
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA;
| | - Miriam Jacome-Sosa
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA;
| | - Nada A Abumrad
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA; .,Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA
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Cifarelli V, Peche VS, Abumrad NA. Vascular and lymphatic regulation of gastrointestinal function and disease risk. Biochim Biophys Acta Mol Cell Biol Lipids 2022; 1867:159207. [PMID: 35882297 PMCID: PMC9642046 DOI: 10.1016/j.bbalip.2022.159207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 06/17/2022] [Accepted: 07/07/2022] [Indexed: 11/29/2022]
Abstract
The vascular and lymphatic systems in the gut regulate lipid transport while restricting transfer of commensal gut microbiota and directing immune cell trafficking. Increased permeability of the endothelial systems in the intestine associates with passage of antigens and microbiota from the gut into the bloodstream leading to tissue inflammation, the release of pro-inflammatory mediators and ultimately to abnormalities of systemic metabolism. Recent studies show that lipid metabolism maintains homeostasis and function of intestinal blood and lymphatic endothelial cells, BECs and LECs, respectively. This review highlights recent progress in this area, and information related to the contribution of the lipid transporter CD36, abundant in BECs and LECs, to gastrointestinal barrier integrity, inflammation, and to gut regulation of whole body metabolism. The potential role of endothelial lipid delivery in epithelial tissue renewal after injury and consequently in the risk of gastric and intestinal diseases is also discussed.
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Affiliation(s)
- Vincenza Cifarelli
- Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA.
| | - Vivek S Peche
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Nada A Abumrad
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
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10
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Chelu A, Williams SG, Keavney BD, Talavera D. Joint analysis of functionally related genes yields further candidates associated with Tetralogy of Fallot. J Hum Genet 2022; 67:613-615. [PMID: 35718831 PMCID: PMC7613636 DOI: 10.1038/s10038-022-01051-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 11/09/2022]
Abstract
Although several genes involved in the development of Tetralogy of Fallot have been identified, no genetic diagnosis is available for the majority of patients. Low statistical power may have prevented the identification of further causative genes in gene-by-gene survey analyses. Thus, bigger samples and/or novel analytic approaches may be necessary. We studied if a joint analysis of groups of functionally related genes might be a useful alternative approach. Our reanalysis of whole-exome sequencing data identified 12 groups of genes that exceedingly contribute to the burden of Tetralogy of Fallot. Further analysis of those groups showed that genes with high-impact variants tend to interact with each other. Thus, our results strongly suggest that additional candidate genes may be found by studying the protein interaction network of known causative genes. Moreover, our results show that the joint analysis of functionally related genes can be a useful complementary approach to classical single-gene analyses.
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Affiliation(s)
- Alexandru Chelu
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Simon G Williams
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Bernard D Keavney
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - David Talavera
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
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11
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Touré M, Hichami A, Sayed A, Suliman M, Samb A, Khan NA. Association between polymorphisms and hypermethylation of CD36 gene in obese and obese diabetic Senegalese females. Diabetol Metab Syndr 2022; 14:117. [PMID: 35982478 PMCID: PMC9386198 DOI: 10.1186/s13098-022-00881-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 07/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Obesity and related metabolic disorders are associated with genetic and epigenetic alterations. In this study, we have examined the association between polymorphisms and hypermethylation of the CD36 gene promoter with obesity in Senegalese females with or without type 2 diabetes mellitus to identify novel molecular markers of these pathologies (obesity and type 2 diabetes mellitus). MATERIALS AND METHODS The study was conducted in Senegal with healthy lean control, obese, and obese diabetic (age; 49.98 years ± 7.52 vs 50.50 years ± 8.76 vs 51.06 ± 5.78, and body mass index (BMI); 24.19 kg/m2 ± 2.74 vs 34.30 kg/m2 ± 4.41 vs 33.09 kg/m2 ± 4.30). We determined three genetic polymorphisms of CD36 i.e., rs1761667, rs1527483, and rs3211867 by real-time polymerase chain reaction, and methylation of CPG islands of CD36 was assessed by methylation-specific polymerase chain reaction (MS-PCR) in DNA isolated from peripheral blood of each participant. Plasma sCD36 levels and DNA methyltransferase 3a (DNMT3a) levels were determined by enzyme-linked immunosorbent assay (ELISA). According to the standard laboratory protocol, all biochemical parameters were analyzed from fasting serum or plasma. RESULTS For rs1761667, obese and obese diabetic subjects had statistically significant different parameters depending on the genotypic distribution. These were waist size for obese and HDL cholesterol for obese diabetic, they were significantly higher in subjects harboring GG genotype of rs1761667 (respectively p = 0.04 and p = 0.04). For rs3211867, obese subjects harboring the AA/AC genotype had significantly higher BMI (p = 0.02) and total cholesterol (p = 0.03) than obese subjects harboring the CC genotype. At the same time, the obese diabetic subjects harboring the AA/AC genotype had total cholesterol levels significantly higher than the obese diabetic subjects harboring the CC genotype (p = 0.03). For rs1527483, only the control subjects had statistically significant different parameters depending on the genotypic distribution. The control subjects harboring the GG genotype had a significantly higher BMI than the control subjects harboring the AA/AG genotype (p = 0.003). The CD36 gene methylation was significantly 1.36 times more frequent in obese and obese diabetic compared to lean control (RR = 1.36; p = 0.04). DNMT3a levels were higher in subjects with CD36 gene methylation than in subjects without CD36 gene methylation in each group. Obese diabetic subjects with CD36 gene methylation had significantly fewer plasmas sCD36 (p = 0.03) and more LDL-cholesterol (p = 0.01) than obese diabetic subjects without CD36 gene methylation. In the control group, an increase in sCD36 levels would be associated with a decrease in total cholesterol and triglyceride levels (coef = -7647.56 p = 0.01 and coef = -2528.50 p = 0.048, respectively) would be associated with an increase in LDL cholesterol levels. For the obese group, an increase in sCD36 levels would be associated with an increase in fasting insulin levels (coef = 490.99 p = 0.02) and a decrease in glycated hemoglobin levels (coef = -1196.26 p = 0.03). An increase in the sCD36 levels would be associated with an increase in the triglyceride levels in the obese diabetic group (coef = 9937.41 p = 0.02). The AA/AC genotype of SNP rs3211867 polymorphism was significantly associated with CD36 gene methylation in the control and obese diabetic groups (respectively p = 0.05, p = 0.002; 95% CI). CONCLUSION These observations suggest that polymorphisms and epigenetic changes in CD36 gene promoters may be implicated in the onset of obesity and its related complication type 2 diabetes mellitus.
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Affiliation(s)
- Maïmouna Touré
- Laboratoire de Physiologie Humaine et d'Explorations Fonctionnelles, Faculté de Médecine, de Pharmacie et d'Odonto-Stomatologie (FMPOS) de l'Université Cheikh Anta Diop (UCAD), Dakar, Sénégal.
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France.
- IRL3189 ESS (Environnement, Santé, Sociétés ), CNRS, CNRST, Bamoko-UCAD, Dakar, Sénégal.
| | - Aziz Hichami
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
| | - Amira Sayed
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
| | - Muhtadi Suliman
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
| | - Abdoulaye Samb
- Laboratoire de Physiologie Humaine et d'Explorations Fonctionnelles, Faculté de Médecine, de Pharmacie et d'Odonto-Stomatologie (FMPOS) de l'Université Cheikh Anta Diop (UCAD), Dakar, Sénégal
- IRL3189 ESS (Environnement, Santé, Sociétés ), CNRS, CNRST, Bamoko-UCAD, Dakar, Sénégal
| | - Naim Akhtar Khan
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
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12
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Miao Z, Chen GD, Huo S, Fu Y, Wu MY, Xu F, Jiang Z, Tang J, Gou W, Xiao C, Liu YP, Wu YY, Sun TY, Sun L, Shen LR, Lin X, Chen YM, Zheng JS. Interaction of n-3 polyunsaturated fatty acids with host CD36 genetic variant for gut microbiome and blood lipids in human cohorts. Clin Nutr 2022; 41:1724-1734. [DOI: 10.1016/j.clnu.2022.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/24/2022] [Accepted: 05/30/2022] [Indexed: 11/27/2022]
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13
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Yazdanpanah Z, Mozaffari-Khosravi H, Mirzaei M, Sheikhha MH, Salehi-Abargouei A. A systematic review and meta-analysis on the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors in adults. Sci Rep 2022; 12:5916. [PMID: 35396566 PMCID: PMC8993862 DOI: 10.1038/s41598-022-09908-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 03/21/2022] [Indexed: 12/04/2022] Open
Abstract
The cluster of differentiation 36 (CD36) is one of the main receptors implicated in the pathogenesis of the cardiovascular disease. This study aimed to assess the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors including body mass index (BMI), waist circumference (WC), total cholesterol (TC), triglyceride, HDL-C, LDL-C, blood pressure and fasting blood glucose (FBG). PubMed, EMBASE, Scopus, web of science, and Google Scholar were searched up to December 2021. Subgroup and meta-regression analyses were conducted to explore sources of heterogeneity. Eighteen eligible studies (6317 participants) were included in the study. In the overall analysis, a significant association was found between rs1761667 polymorphism of CD36 and TG in allelic (p < 0.001), recessive (p = 0.001) and homozygous (p = 0.006) models. A relationship between this polymorphism and HDL-C and FBG level was observed in the recessive genetic model. In the subgroup analysis, the A allele was associated with impaired lipid profiles (TC, LDL-C and HDL-C) in the Asian population. The influences of health status, design of the study, confounders, and other sources of heterogeneity should be considered when interpreting present findings. Cohort studies with large sample size and in different ethnicities are needed to confirm the relationship between rs1761667 SNP and cardiometabolic risk factors.
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Affiliation(s)
- Zeinab Yazdanpanah
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, PO Code 8915173160, Iran
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, PO Code 8915173160, Iran
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Mirzaei
- Yazd Cardiovascular Research Centre, Non-Communicable Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Hasan Sheikhha
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, PO Code 8915173160, Iran.
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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14
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Abstract
During the last couples of years, a number of studies have increasingly accumulated on the gustatory perception of dietary fatty acids in rodent models and human beings in health and disease. There is still a debate to coin a specific term for the gustatory perception of dietary fatty acids either as the sixth basic taste quality or as an alimentary taste. Indeed, the psycho-physical cues of orosensory detection of dietary lipids are not as distinctly perceived as other taste qualities like sweet or bitter. The cellular and molecular pharmacological mechanisms, triggered by the binding of dietary long-chain fatty acids (LCFAs) to tongue taste bud lipid receptors like CD36 and GPR120, involve Ca2+ signaling as other five basic taste qualities. We have not only elucidated the role of Ca2+ signaling but also identified different components of the second messenger cascade like STIM1 and MAP kinases, implicated in fat taste perception. We have also demonstrated the implication of Calhm1 voltage-gated channels and store-operated Ca2+ (SOC) channels like Orai1, Orai1/3, and TRPC3 in gustatory perception of dietary fatty acids. We have not only employed siRNA technology in vitro and ex vivo on tissues but also used animal models of genetic invalidation of STIM1, ERK1, Orai1, Calhm1 genes to explore their implications in fat taste signal transduction. Moreover, our laboratory has also demonstrated the importance of LCFAs detection dysfunction in obesity in animal models and human beings.
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Affiliation(s)
- Aziz Hichami
- Physiologie de la Nutrition and Toxicologie (NUTox), UMR1231 INSERM/Université de Bourgogne, Dijon, France
| | - Amira Sayed Khan
- Physiologie de la Nutrition and Toxicologie (NUTox), UMR1231 INSERM/Université de Bourgogne, Dijon, France
| | - Naim Akhtar Khan
- Physiologie de la Nutrition and Toxicologie (NUTox), UMR1231 INSERM/Université de Bourgogne, Dijon, France.
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15
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Wade G, McGahee A, Ntambi JM, Simcox J. Lipid Transport in Brown Adipocyte Thermogenesis. Front Physiol 2021; 12:787535. [PMID: 35002769 PMCID: PMC8733649 DOI: 10.3389/fphys.2021.787535] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/02/2021] [Indexed: 12/30/2022] Open
Abstract
Non-shivering thermogenesis is an energy demanding process that primarily occurs in brown and beige adipose tissue. Beyond regulating body temperature, these thermogenic adipocytes regulate systemic glucose and lipid homeostasis. Historically, research on thermogenic adipocytes has focused on glycolytic metabolism due to the discovery of active brown adipose tissue in adult humans through glucose uptake imaging. The importance of lipids in non-shivering thermogenesis has more recently been appreciated. Uptake of circulating lipids into thermogenic adipocytes is necessary for body temperature regulation and whole-body lipid homeostasis. A wide array of circulating lipids contribute to thermogenic potential including free fatty acids, triglycerides, and acylcarnitines. This review will summarize the mechanisms and regulation of lipid uptake into brown adipose tissue including protein-mediated uptake, lipoprotein lipase activity, endocytosis, vesicle packaging, and lipid chaperones. We will also address existing gaps in knowledge for cold induced lipid uptake into thermogenic adipose tissue.
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Affiliation(s)
| | | | | | - Judith Simcox
- Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, United States
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16
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Mistry JJ, Hellmich C, Moore JA, Jibril A, Macaulay I, Moreno-Gonzalez M, Di Palma F, Beraza N, Bowles KM, Rushworth SA. Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection. Nat Commun 2021; 12:7130. [PMID: 34880245 PMCID: PMC8655073 DOI: 10.1038/s41467-021-27460-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 11/23/2021] [Indexed: 11/09/2022] Open
Abstract
Acute infection is known to induce rapid expansion of hematopoietic stem cells (HSCs), but the mechanisms supporting this expansion remain incomplete. Using mouse models, we show that inducible CD36 is required for free fatty acid uptake by HSCs during acute infection, allowing the metabolic transition from glycolysis towards β-oxidation. Mechanistically, high CD36 levels promote FFA uptake, which enables CPT1A to transport fatty acyl chains from the cytosol into the mitochondria. Without CD36-mediated FFA uptake, the HSCs are unable to enter the cell cycle, subsequently enhancing mortality in response to bacterial infection. These findings enhance our understanding of HSC metabolism in the bone marrow microenvironment, which supports the expansion of HSCs during pathogenic challenge.
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Affiliation(s)
- Jayna J Mistry
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK.,Earlham Institute, Norwich Research Park, Norwich, NR4 7UH, UK
| | - Charlotte Hellmich
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK.,Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich, NR4 7UY, UK
| | - Jamie A Moore
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK
| | - Aisha Jibril
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK
| | - Iain Macaulay
- Earlham Institute, Norwich Research Park, Norwich, NR4 7UH, UK
| | - Mar Moreno-Gonzalez
- Gut Microbes and Health Institute Strategic Programme, Quadram Institute, Norwich, UK
| | - Federica Di Palma
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK
| | - Naiara Beraza
- Gut Microbes and Health Institute Strategic Programme, Quadram Institute, Norwich, UK.
| | - Kristian M Bowles
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK. .,Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich, NR4 7UY, UK.
| | - Stuart A Rushworth
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK.
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17
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Jacome-Sosa M, Miao ZF, Peche VS, Morris EF, Narendran R, Pietka KM, Samovski D, Lo HYG, Pietka T, Varro A, Love-Gregory L, Goldenring JR, Kuda O, Gamazon ER, Mills JC, Abumrad NA. CD36 maintains the gastric mucosa and associates with gastric disease. Commun Biol 2021; 4:1247. [PMID: 34728772 PMCID: PMC8563937 DOI: 10.1038/s42003-021-02765-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 10/06/2021] [Indexed: 12/19/2022] Open
Abstract
The gastric epithelium is often exposed to injurious elements and failure of appropriate healing predisposes to ulcers, hemorrhage, and ultimately cancer. We examined the gastric function of CD36, a protein linked to disease and homeostasis. We used the tamoxifen model of gastric injury in mice null for Cd36 (Cd36-/-), with Cd36 deletion in parietal cells (PC-Cd36-/-) or in endothelial cells (EC-Cd36-/-). CD36 expresses on corpus ECs, on PC basolateral membranes, and in gastrin and ghrelin cells. Stomachs of Cd36-/- mice have altered gland organization and secretion, more fibronectin, and inflammation. Tissue respiration and mitochondrial efficiency are reduced. Phospholipids increased and triglycerides decreased. Mucosal repair after injury is impaired in Cd36-/- and EC-Cd36-/-, not in PC-Cd36-/- mice, and is due to defect of progenitor differentiation to PCs, not of progenitor proliferation or mature PC dysfunction. Relevance to humans is explored in the Vanderbilt BioVu using PrediXcan that links genetically-determined gene expression to clinical phenotypes, which associates low CD36 mRNA with gastritis, gastric ulcer, and gastro-intestinal hemorrhage. A CD36 variant predicted to disrupt an enhancer site associates (p < 10-17) to death from gastro-intestinal hemorrhage in the UK Biobank. The findings support role of CD36 in gastric tissue repair, and its deletion associated with chronic diseases that can predispose to malignancy.
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Affiliation(s)
- Miriam Jacome-Sosa
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
| | - Zhi-Feng Miao
- Department of Surgical Oncology, Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, First Hospital of China Medical University, Shenyang, China
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Vivek S Peche
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Edward F Morris
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Ramkumar Narendran
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Kathryn M Pietka
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Dmitri Samovski
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Hei-Yong G Lo
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Terri Pietka
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Andrea Varro
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Latisha Love-Gregory
- Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO, USA
| | - James R Goldenring
- Departments of Surgery and Cell and Developmental Biology, Vanderbilt University Medical Center and VA Medical Center, Nashville, TN, USA
| | - Ondrej Kuda
- Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague 4, Czech Republic
| | - Eric R Gamazon
- Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Jason C Mills
- Gastroenterology & Hepatology Section, Departments of Medicine and of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
| | - Nada A Abumrad
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
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18
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Cifarelli V, Appak-Baskoy S, Peche VS, Kluzak A, Shew T, Narendran R, Pietka KM, Cella M, Walls CW, Czepielewski R, Ivanov S, Randolph GJ, Augustin HG, Abumrad NA. Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells. Nat Commun 2021; 12:3350. [PMID: 34099721 PMCID: PMC8184948 DOI: 10.1038/s41467-021-23808-3] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 05/13/2021] [Indexed: 12/18/2022] Open
Abstract
Disruption of lymphatic lipid transport is linked to obesity and type 2 diabetes (T2D), but regulation of lymphatic vessel function and its link to disease remain unclear. Here we show that intestinal lymphatic endothelial cells (LECs) have an increasing CD36 expression from lymphatic capillaries (lacteals) to collecting vessels, and that LEC CD36 regulates lymphatic integrity and optimizes lipid transport. Inducible deletion of CD36 in LECs in adult mice (Cd36ΔLEC) increases discontinuity of LEC VE-cadherin junctions in lacteals and collecting vessels. Cd36ΔLEC mice display slower transport of absorbed lipid, more permeable mesenteric lymphatics, accumulation of inflamed visceral fat and impaired glucose disposal. CD36 silencing in cultured LECs suppresses cell respiration, reduces VEGF-C-mediated VEGFR2/AKT phosphorylation and destabilizes VE-cadherin junctions. Thus, LEC CD36 optimizes lymphatic junctions and integrity of lymphatic lipid transport, and its loss in mice causes lymph leakage, visceral adiposity and glucose intolerance, phenotypes that increase risk of T2D. Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.
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Affiliation(s)
- Vincenza Cifarelli
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA.
| | - Sila Appak-Baskoy
- European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.,Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany
| | - Vivek S Peche
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Andrew Kluzak
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Trevor Shew
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Ramkumar Narendran
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Kathryn M Pietka
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Marina Cella
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Curtis W Walls
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA
| | - Rafael Czepielewski
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Stoyan Ivanov
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Gwendalyn J Randolph
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, USA
| | - Hellmut G Augustin
- European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.,Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany
| | - Nada A Abumrad
- Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, USA. .,Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, USA.
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19
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Common variants in the CD36 gene are associated with dietary fat intake, high-fat food consumption and serum triglycerides in a cohort of Quebec adults. Int J Obes (Lond) 2021; 45:1193-1202. [PMID: 33574567 DOI: 10.1038/s41366-021-00766-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 12/03/2020] [Accepted: 01/20/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND The CD36 gene is a candidate for sensory detection of fatty acids and has been associated with individual differences in fat preferences and consumption. Excess adiposity may compromise sensory detection, but few studies have examined whether associations between CD36 variants and fat consumption differ between underweight/normal weight (UW/NW) and overweight/obese (OW/OB) individuals. METHODS Diet (assessed by food frequency questionnaire), genetic (nine variants), body mass index (BMI), lifestyle and biomarker data were obtained from the CARTaGENE biobank (n = 12,065), a Quebec cohort of middle-aged adults. Primary outcome variables included intakes (%kcal/day) of total, saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids. Secondary outcome variables included consumption (servings/day) of four food categories with high-fat content (added fats and oils, high-fat foods, desserts and MUFA- and PUFA-rich foods) and biomarkers of chronic disease. Multivariable regression models stratified by BMI category were used to assess associations between CD36 variants and outcome variables. RESULTS Among UW/NW, rs1049654 and rs10499859 were associated with higher intakes of total fat, MUFA and PUFA (all P < 0.05), while rs1527483 and rs3211956 were associated with higher SFA (P = 0.0278) and lower PUFA (P = 0.0466) intake, respectively. Rs1527483 and rs3211956 were also associated with higher consumption of high-fat foods and desserts (all P < 0.05). Among OW, rs1054516 and rs3173798 were associated with higher SFA intake (both P < 0.05), and rs1054516 was also associated with higher serum triglycerides (P = 0.0065). CONCLUSIONS CD36 variants are associated with habitual fat consumption, which may play a role in subsequent associations with chronic-disease biomarkers. Associations differ by BMI status and dietary fat type.
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20
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Yang H, Tan S, Chen S, Wu Y, Yang Y, Li H, Yu H. Effects of fermented Yupingfeng on intramuscular fatty acids and ruminal microbiota in Qingyuan black goats. Anim Sci J 2021; 92:e13554. [PMID: 33938087 DOI: 10.1111/asj.13554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 03/05/2021] [Accepted: 03/15/2021] [Indexed: 11/29/2022]
Abstract
Our previous work has demonstrated that Yupingfeng, a Chinese herb medicine, considered as prebiotic showed beneficial properties in poultry health and disease prevention and regulated intestinal microbiota. The effects of Yupingfeng on fatty acids related to meat flavor and ruminal microbiota are not yet known in Qingyuan black goat. In this study, we supplemented fermented (FYP) and unfermented (UYP) Yupingfeng in different combinations to 90 goats. Compared with the normal control group, FYP and UYP significantly increased the concentration of palmitic acid, octadecanoic acid, and arachidonate acid (related to meat flavor) in the longissimus dorsi muscle (p < .05). In addition, the significant upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid translocase (CD36) was observed in the FYP and UYP groups (p < .05). In addition, Firmicutes and Bacteroidetes were the most abundance in goat rumen. At the genus level, FYP and UYP significantly increased Ruminococcus related to fiber degradation, and Alistipes related to short-chain fatty acids production. In summary, Yupingfeng could improve fatty acids of goat meat, which is probably triggered by the increase of PPARγ and CD36, and microbial activity. Besides, FYP showed more beneficial effects than UYP, with increased flavor fatty acids and beneficial microbes.
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Affiliation(s)
- Hong Yang
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
| | - Shuwen Tan
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
| | - Siyu Chen
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
| | - Yongliang Wu
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
| | - Ying Yang
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
| | - Hua Li
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
| | - Hui Yu
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China
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Connor T, McPhillips M, Hipwell M, Ziolkowski A, Oldmeadow C, Clapham M, Pockney PG, Lis E, Banasiewicz T, Pławski A, Scott RJ. CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC. Hered Cancer Clin Pract 2021; 19:25. [PMID: 33926505 PMCID: PMC8086281 DOI: 10.1186/s13053-021-00183-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 04/20/2021] [Indexed: 12/30/2022] Open
Abstract
Background Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes patients to colorectal cancer. FAP is the result of a loss of APC function due to germline pathogenic variants disrupting gene expression. Genotype-phenotype correlations are described for FAP. For example attenuated forms of the disease are associated with pathogenic variants at the 5’ and 3’ ends of APC whilst severe forms of the disease appear to be linked to variants occurring in the mutation cluster region (MCR) of the gene. Variants occurring in the MCR are phenotypically associated with hundreds to thousands of adenomas carpeting the colon and rectum and patients harbouring changes in this region have a high propensity to develop colorectal cancer. Not all patients who carry pathogenic variants in this region have severe disease which may be a result of environmental factors. Alternatively, phenotypic variation observed in these patients could be due to modifier genes that either promote or inhibit disease expression. Mouse models of FAP have provided several plausible candidate modifier genes, but very few of these have survived scrutiny. One such genetic modifier that appears to be associated with disease expression is CD36. We previously reported a weak association between a polymorphism in CD36 and a later age of disease onset on a relatively small FAP patient cohort. Methods In the current study, we enlarged the FAP cohort. 395 patients all carrying pathogenic variants in APC were tested against three CD36 Single Nucleotide Polymorphisms (SNP)s (rs1049673, rs1761667 rs1984112), to determine if any of them were associated with differences in the age of disease expression. Results Overall, there appeared to be a statistically significant difference in the age of disease onset between carriers of the variant rs1984112 and wildtype. Furthermore, test equality of survivor functions for each SNP and mutation group suggested an interaction in the Log Rank, Wilcoxon, and Tarone-Ware methods for rs1049673, rs1761667, and rs1984112, thereby supporting the notion that CD36 modifies disease expression. Conclusions This study supports and strengthens our previous findings concerning CD36 and an association with disease onset in FAP, AFAP and FAP-MCR affected individuals. Knowledge about the role CD36 in adenoma development may provide greater insight into the development of colorectal cancer.
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Affiliation(s)
- T Connor
- School of Biomedical Sciences, Faculty of Health, University of Newcastle, Callaghan Campus, NSW, 2308, Newcastle, Australia
| | - M McPhillips
- Division of Molecular Medicine, NSW Health Pathology North, 2305, New Lambton, NSW, Australia
| | - M Hipwell
- Division of Molecular Medicine, NSW Health Pathology North, 2305, New Lambton, NSW, Australia
| | - A Ziolkowski
- Division of Molecular Medicine, NSW Health Pathology North, 2305, New Lambton, NSW, Australia
| | - C Oldmeadow
- Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW, Australia
| | - M Clapham
- Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW, Australia
| | - P G Pockney
- Department of Surgery, John Hunter Hospital, Newcastle, Australia
| | - E Lis
- Department of General, Endocrinological Surgery and Gastroenterological Oncology, Poznan University of Medical Sciences, Poznan, Poland.,Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
| | - T Banasiewicz
- Department of General, Endocrinological Surgery and Gastroenterological Oncology, Poznan University of Medical Sciences, Poznan, Poland
| | - A Pławski
- Department of General, Endocrinological Surgery and Gastroenterological Oncology, Poznan University of Medical Sciences, Poznan, Poland.,Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
| | - R J Scott
- School of Biomedical Sciences, Faculty of Health, University of Newcastle, Callaghan Campus, NSW, 2308, Newcastle, Australia. .,Division of Molecular Medicine, NSW Health Pathology North, 2305, New Lambton, NSW, Australia. .,Hunter Medical Research Institute, John Hunter Hospital, 2305, New Lambton, NSW, Australia.
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22
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Single nucleotide polymorphism in CD36: Correlation to peptide YY levels in obese and non-obese adults. Clin Nutr 2021; 40:2707-2715. [PMID: 33933736 DOI: 10.1016/j.clnu.2021.02.044] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 02/18/2021] [Accepted: 02/28/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND & AIMS Human beings are often driven to exhibit dietary preference according to their hedonic characteristics. Though previous studies proposed that the fat taste preference of an obese individual was associated with BMI, the perception of fat taste differs for every individual. The genetic variation among populations in taste receptor genes such as CD36 may be a contributing factor for this difference. Satiety peptides can also play a role in the regulation of fat taste perception. Generally, this hormone helps us to feel the sense of satiety. METHODS We have analysed the relationship among oro-gustatory perception of dietary lipids, salivary peptide-YY and genetic polymorphism in CD36. Oral fatty acid sensitivity analysis was performed by alternative forced choice method. Salivary peptide-YY concentration was analysed by ELISA and single nucleotide polymorphism (SNP) in CD36 gene was determined by Real-Time PCR experiments. RESULTS We observed that the SNP at rs1761667 of CD36 and oral detection threshold for linoleic acid (LA) are associated with choice of food, lipid profiles, peptide-YY as well as adiposity parameters in obese population. Obese peoples had significantly low levels of peptide YY than people with BMI less than 25. These factors possibly play a role in preference for energy rich diets, development of obesity and associated complications. CONCLUSION This study provides a solid foundation for understanding the alterations in the dietary fat intake and levels of peptide-YY, which are associated with polymorphism in fat taste receptor. This is the first report that shows a significant relationship between the satiety hormone level, SNP in CD36 gene and oral fat detection threshold in human subjects.
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23
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Mineo C. Lipoprotein receptor signalling in atherosclerosis. Cardiovasc Res 2021; 116:1254-1274. [PMID: 31834409 DOI: 10.1093/cvr/cvz338] [Citation(s) in RCA: 106] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 11/01/2019] [Accepted: 12/10/2019] [Indexed: 12/11/2022] Open
Abstract
The founding member of the lipoprotein receptor family, low-density lipoprotein receptor (LDLR) plays a major role in the atherogenesis through the receptor-mediated endocytosis of LDL particles and regulation of cholesterol homeostasis. Since the discovery of the LDLR, many other structurally and functionally related receptors have been identified, which include low-density lipoprotein receptor-related protein (LRP)1, LRP5, LRP6, very low-density lipoprotein receptor, and apolipoprotein E receptor 2. The scavenger receptor family members, on the other hand, constitute a family of pattern recognition proteins that are structurally diverse and recognize a wide array of ligands, including oxidized LDL. Among these are cluster of differentiation 36, scavenger receptor class B type I and lectin-like oxidized low-density lipoprotein receptor-1. In addition to the initially assigned role as a mediator of the uptake of macromolecules into the cell, a large number of studies in cultured cells and in in vivo animal models have revealed that these lipoprotein receptors participate in signal transduction to modulate cellular functions. This review highlights the signalling pathways by which these receptors influence the process of atherosclerosis development, focusing on their roles in the vascular cells, such as macrophages, endothelial cells, smooth muscle cells, and platelets. Human genetics of the receptors is also discussed to further provide the relevance to cardiovascular disease risks in humans. Further knowledge of the vascular biology of the lipoprotein receptors and their ligands will potentially enhance our ability to harness the mechanism to develop novel prophylactic and therapeutic strategies against cardiovascular diseases.
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Affiliation(s)
- Chieko Mineo
- Department of Pediatrics and Cell Biology, Center for Pulmonary and Vascular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA
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Abumrad NA, Cabodevilla AG, Samovski D, Pietka T, Basu D, Goldberg IJ. Endothelial Cell Receptors in Tissue Lipid Uptake and Metabolism. Circ Res 2021; 128:433-450. [PMID: 33539224 DOI: 10.1161/circresaha.120.318003] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Lipid uptake and metabolism are central to the function of organs such as heart, skeletal muscle, and adipose tissue. Although most heart energy derives from fatty acids (FAs), excess lipid accumulation can cause cardiomyopathy. Similarly, high delivery of cholesterol can initiate coronary artery atherosclerosis. Hearts and arteries-unlike liver and adrenals-have nonfenestrated capillaries and lipid accumulation in both health and disease requires lipid movement from the circulation across the endothelial barrier. This review summarizes recent in vitro and in vivo findings on the importance of endothelial cell receptors and uptake pathways in regulating FAs and cholesterol uptake in normal physiology and cardiovascular disease. We highlight clinical and experimental data on the roles of ECs in lipid supply to tissues, heart, and arterial wall in particular, and how this affects organ metabolism and function. Models of FA uptake into ECs suggest that receptor-mediated uptake predominates at low FA concentrations, such as during fasting, whereas FA uptake during lipolysis of chylomicrons may involve paracellular movement. Similarly, in the setting of an intact arterial endothelial layer, recent and historic data support a role for receptor-mediated processes in the movement of lipoproteins into the subarterial space. We conclude with thoughts on the need to better understand endothelial lipid transfer for fuller comprehension of the pathophysiology of hyperlipidemia, and lipotoxic diseases such as some forms of cardiomyopathy and atherosclerosis.
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Affiliation(s)
- Nada A Abumrad
- Division of Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Saint Louis, MO (N.A.A., D.S., T.P.)
| | - Ainara G Cabodevilla
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine (A.G.C., D.B., I.J.G.)
| | - Dmitri Samovski
- Division of Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Saint Louis, MO (N.A.A., D.S., T.P.)
| | - Terri Pietka
- Division of Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Saint Louis, MO (N.A.A., D.S., T.P.)
| | - Debapriya Basu
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine (A.G.C., D.B., I.J.G.)
| | - Ira J Goldberg
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine (A.G.C., D.B., I.J.G.)
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Contribution of rs3211938 polymorphism at CD36 to glucose levels, oxidized low-density lipoproteins, insulin resistance, and body mass index in Mexican mestizos with type-2 diabetes from western Mexico. NUTR HOSP 2021; 38:742-748. [PMID: 33966442 DOI: 10.20960/nh.03447] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Introduction Background: type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance (IR), and abnormal fatty acid metabolism in which the CD36 receptor has been implicated in glucose and lipid dysregulation. Objective: to evaluate the contribution of polymorphism CD36 rs3211938 to metabolic profile in T2DM Mexican mestizos from western Mexico. Methods: we included 115 individuals classified as non-T2DM (NT2DM) adults and T2DM patients. Polymorphism CD36 rs3211938 was assessed by PCR-RFLP. Anthropometric and metabolic markers were measured by routine methods, and insulin and oxidized LDL (ox-LDL) were measured by ELISA. Results: the distribution of genotypes between NT2DM and T2DM patients was different (p < 0.001), as was the allele frequency (p = 0.002). NT2DM TG carriers showed the lowest levels of basal insulin and HOMA-IR index in comparison with TT carriers (p < 0.05 and p < 0.05, respectively). In the T2DM group TG carriers showed high BMI, WHR, and weight values (p = 0.001; p ≤ 0.05 and p < 0.05, respectively), and the highest levels of basal glucose, HDL-cholesterol, ox-LDL, and HOMA-IR (p < 0.001; p < 0.001; p < 0.001, and p = 0.001, respectively) in comparison with diabetic TT carriers. Conclusion: the CD36 rs3211938 TG genotype is associated with high levels of glucose, ox-LDL, HDL-cholesterol, and IR, and with increased BMI in Mexican mestizo T2DM patients from western Mexico.
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Tang ZZ, Sliwoski GR, Chen G, Jin B, Bush WS, Li B, Capra JA. PSCAN: Spatial scan tests guided by protein structures improve complex disease gene discovery and signal variant detection. Genome Biol 2020; 21:217. [PMID: 32847609 PMCID: PMC7448521 DOI: 10.1186/s13059-020-02121-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 07/27/2020] [Indexed: 12/25/2022] Open
Abstract
Germline disease-causing variants are generally more spatially clustered in protein 3-dimensional structures than benign variants. Motivated by this tendency, we develop a fast and powerful protein-structure-based scan (PSCAN) approach for evaluating gene-level associations with complex disease and detecting signal variants. We validate PSCAN's performance on synthetic data and two real data sets for lipid traits and Alzheimer's disease. Our results demonstrate that PSCAN performs competitively with existing gene-level tests while increasing power and identifying more specific signal variant sets. Furthermore, PSCAN enables generation of hypotheses about the molecular basis for the associations in the context of protein structures and functional domains.
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Affiliation(s)
- Zheng-Zheng Tang
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, 53715 WI USA
- Wisconsin Institute for Discovery, Madison, 53715 WI USA
| | - Gregory R. Sliwoski
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, 37232 TN USA
| | - Guanhua Chen
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, 53715 WI USA
| | - Bowen Jin
- Department for Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106 OH USA
| | - William S. Bush
- Department for Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106 OH USA
- Institute for Computational Biology, Case Western Reserve University, Cleveland, 44106 OH USA
| | - Bingshan Li
- Department of Molecular Physiology & Biophysics, Vanderbilt University Medical Center, Nashville, 37232 TN USA
| | - John A. Capra
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, 37232 TN USA
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, 37232 TN USA
- Departments of Biological Sciences and Computer Science, Vanderbilt University, Nashville, 37232 TN USA
- Center for Structural Biology, Vanderbilt University, Nashville, 37232 TN USA
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Du Y, Chen K, Liu E, Wang X, Li F, Liu T, Zheng X, Li G, Che J. Gender-specific associations of CD36 polymorphisms with the lipid profile and susceptibility to premature multi-vessel coronary artery heart disease in the Northern Han Chinese. Gene 2020; 753:144806. [PMID: 32461018 DOI: 10.1016/j.gene.2020.144806] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 05/15/2020] [Accepted: 05/21/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND The aim of the present study was to detect potential gender-specific associations between some common CD36 single nucleotide polymorphisms (SNPs) and the lipid profile, as well as the susceptibility to premature multi-vessel coronary artery heart disease (CHD) in the Han population of Northern China. METHODS A systematic three-step study process was employed to detect associations between CD36 gene variants and blood lipid profiles, as well as premature multi-vessel CHD in a gender-specific manner. RESULTS The current study documented the following novel findings: (I) the full population-based association study in 329 Northern Han Chinese showed that four common CD36 polymorphisms were significantly related to extreme lipid profiles, with statistically significant effects based on gender interactions (rs1049673: P = 0.001; rs7755: P = 0.008; rs3211956: P = 0.034; and rs3173798: P = 0.004); (ii) these statistically significant effects could be decomposed into statistically significant atherogenic effects in males, but non-significant non-atherogenic effects in females; (iii) the results of logistic regression analysis indicated that current smoking status, low density lipoprotein cholesterol (LDL-C) levels, and type-2 diabetes were independent risk factors for premature multi-vessel CHD phenotype (P < 0.0001). CONCLUSIONS Four common CD36 polymorphisms (rs1049673, rs7755, rs3211956, and rs3173798) were identified to be significantly associated with extreme lipid profiles and had statistically opposite gender-specific clinical lipid profile effects. Thus, the 3'-untranslated regions (3'-UTR) CD36 SNPs could be a novel target for metabolic abnormalities in males of the Han nationality from Northern China.
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Affiliation(s)
- Yaqin Du
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Kangyin Chen
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Enzhao Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Xuewen Wang
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Feixue Li
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Xintian Zheng
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
| | - Guangping Li
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.
| | - Jingjin Che
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.
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Enciso-Ramírez M, Reyes-Castillo Z, Llamas-Covarrubias MA, Guerrero L, López-Espinoza A, Valdés-Miramontes EH. CD36 gene polymorphism -31118 G > A (rs1761667) is associated with overweight and obesity but not with fat preferences in Mexican children. INT J VITAM NUTR RES 2020; 91:513-521. [PMID: 32419652 DOI: 10.1024/0300-9831/a000656] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
CD36 glycoprotein is a candidate receptor involved in the gustatory detection of lipids and emerging evidence has suggested that genetic variations in CD36 may modulate the oral perception threshold to fatty acids. Here, we analyzed the association of -31118 G > A polymorphism in CD36 gene with nutritional status and preferences for fatty foods in Mexican children. Genotyping of SNP rs1761667 was performed in school-age children (n = 63) in addition to sensory tests evaluating the preference and satisfaction score assigned to oil-based sauces of different fatty acid composition. The G allele was associated with high BMI z-score in children (OR = 2.43, 95% (CI 1.02-5.99); p = 0.02) but CD36 genotypes (AA, GA, and GG) did not show significant association with the preference and satisfaction scores assigned to oil-based sauces. The BMI z-score showed no association with the preference to oil-based sauces; however, children with normal weight gave higher satisfaction scores to sauces with a high content of unsaturated fatty acids than to sauces rich in saturated fatty acids (0.56 ± 1.26 vs. 0.06 ± 1.22; p = 0.02). Therefore, the G allele of -31118 G > A SNP in CD36 gene is associated with overweight and obesity in Mexican children but do not appear to modulate the preferences and satisfaction scores to fat.
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Affiliation(s)
- Mayra Enciso-Ramírez
- Instituto de Investigaciones en Comportamiento Alimentario y Nutrición (IICAN), Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Jalisco, México
| | - Zyanya Reyes-Castillo
- Instituto de Investigaciones en Comportamiento Alimentario y Nutrición (IICAN), Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Jalisco, México
| | - Mara Anaís Llamas-Covarrubias
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Luis Guerrero
- IRTA-Monells, Institut de Recerca i Tecnologia Agroalimentàries, Granja Camps i Armet, Monells, Girona, Spain
| | - Antonio López-Espinoza
- Instituto de Investigaciones en Comportamiento Alimentario y Nutrición (IICAN), Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Jalisco, México
| | - Elia Herminia Valdés-Miramontes
- Instituto de Investigaciones en Comportamiento Alimentario y Nutrición (IICAN), Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Jalisco, México
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Robino A, Concas MP, Catamo E, Gasparini P. A Brief Review of Genetic Approaches to the Study of Food Preferences: Current Knowledge and Future Directions. Nutrients 2019; 11:nu11081735. [PMID: 31357559 PMCID: PMC6722914 DOI: 10.3390/nu11081735] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 07/17/2019] [Accepted: 07/25/2019] [Indexed: 02/07/2023] Open
Abstract
Genetic variation plays a crucial role in individual differences in food preferences which ultimately influence food selection and health. Our current understanding of this pathway has been informed through twin studies (to assess the heritability of food preferences), candidate gene studies, and genome-wide association studies (GWAS). However, most of this literature is mainly focused on genes previously identified as having taste or smell functions. New data suggests that genes not associated with taste or smell perception may be involved in food preferences and contribute to health outcomes. This review highlights these emerging findings and suggests a polygenic risk assessment approach to explore new relationships between food preferences and health risks.
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Affiliation(s)
- Antonietta Robino
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137, Trieste, Italy.
| | - Maria Pina Concas
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137, Trieste, Italy
| | - Eulalia Catamo
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137, Trieste, Italy
| | - Paolo Gasparini
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137, Trieste, Italy
- Department of Medical Sciences, University of Trieste, Strada di Fiume, 447, 34149 Trieste, Italy
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Yasumatsu K, Iwata S, Inoue M, Ninomiya Y. Fatty acid taste quality information via GPR120 in the anterior tongue of mice. Acta Physiol (Oxf) 2019; 226:e13215. [PMID: 30375738 DOI: 10.1111/apha.13215] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/11/2018] [Accepted: 10/24/2018] [Indexed: 12/31/2022]
Abstract
AIM To elucidate whether fatty acid taste has a quality that does not overlap with other primary qualities, we investigated potential neuron types coding fatty acid information and how GPR120 is involved. METHODS Single fibre recordings in the chorda tympani (CT) nerve and behavioural response measurements using a conditioned taste aversion paradigm were performed in GPR120-knockout (KO) and wild-type (WT) mice. RESULTS Single fibres can be classified into fatty acid (F)-, S-, M-, electrolyte (E)-, Q-, and N-type groups according to the maximal response among oleic acid, sucrose, monopotassium glutamate (MPG), HCl, quinine hydrochloride, and NaCl respectively. Among fibres, 4.0% in GPR120-KO and 17.9% in WT mice showed a maximal response to oleic acid (F-type). Furthermore, half or more of S- and M-type fibres showed responses to fatty acids in both mouse strains, although the thresholds in KO mice were significantly higher and impulse frequencies lower than those in WT mice. GPR120-KO mice conditioned to avoid linoleic acid showed generalized stimulus avoidances for MPG, indicating qualitative similarity between linoleic acid and MPG. The KO mice showed a higher generalization threshold for linoleic acid than that of WT mice. CONCLUSION Fatty acid taste is suggested to have a unique quality owing to the discovery of F-type fibres, with GPR120 involved in neural information pathways for a unique quality and palatable taste qualities in the mouse CT nerve. GPR120 plays roles in distinguishing fatty acid taste from other primary tastes and the detection of low linoleic acid concentrations.
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Affiliation(s)
- Keiko Yasumatsu
- Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing Kyushu University Fukuoka Japan
| | - Shusuke Iwata
- Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing Kyushu University Fukuoka Japan
| | - Mayuko Inoue
- Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing Kyushu University Fukuoka Japan
| | - Yuzo Ninomiya
- Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing Kyushu University Fukuoka Japan
- Monell Chemical Senses Center Philadelphia Pennsylvania
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Cluster of differentiation 36 gene polymorphism (rs1761667) is associated with dietary MUFA intake and hypertension in a Japanese population. Br J Nutr 2019; 121:1215-1222. [PMID: 30924431 DOI: 10.1017/s0007114519000679] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cluster of differentiation 36 (CD36) is a membrane receptor expressed on a wide variety of human cells. CD36 polymorphisms are reportedly associated with oral fat perception, dietary intake and metabolic disorders. The present study examined associations of two CD36 polymorphisms (rs1761667 and rs1527483) and dietary fat intake, and metabolic phenotypes in a Japanese population. This cross-sectional study was conducted based on clinical information collected from health check-ups in Japan (n 495). Dietary nutrient intake was estimated from a validated short FFQ and adjusted for total energy intake using the residual method. Mean blood pressure was calculated from systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertension was defined as SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg, or use of antihypertensive drugs. Genotyping was performed using PCR with confronting two-pair primers method. Mean age was 63·4 (sd 9·9) years. Individuals with the AA genotype showed higher total fat and MUFA intake (standardised β = 0·110 and 0·087, P = 0·01 and 0·05, respectively) compared with the GG and GA genotypes. For metabolic phenotypes, the AA genotype of rs1761667 had a lower blood pressure compared with the GG genotype (standardised β = -0·123, P = 0·02). Our results suggested that the AA genotype of rs1761667 in the CD36 gene was associated with higher intake of total fat and MUFA and lower risk of hypertension in a Japanese population.
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Sozen E, Demirel T, Ozer NK. Vitamin E: Regulatory role in the cardiovascular system. IUBMB Life 2019; 71:507-515. [PMID: 30779288 DOI: 10.1002/iub.2020] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 01/24/2019] [Indexed: 12/22/2022]
Abstract
Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality, all around the world. Vitamin E is an important nutrient influencing key cellular and molecular mechanisms as well as gene expression regulation centrally involved in the prevention of CVD. Cell culture and animal studies have focused on the identification of vitamin E regulated signaling pathways and involvement on inflammation, lipid homeostasis, and atherosclerotic plaque stability. While some of these vitamin E functions were verified in clinical trials, some of the positive effects were not translated into beneficial outcomes in epidemiological studies. In recent years, the physiological metabolites of vitamin E, including the liver derived (long- and short-chain) metabolites and phosphorylated (α-, γ-tocopheryl phosphate) forms, have also provided novel mechanistic insight into CVD regulation that expands beyond the vitamin E precursor. It is certain that this emerging insight into the molecular and cellular action of vitamin E will help to design further studies, either in animal models or clinical trials, on the reduction of risk for CVDs. This review focuses on vitamin E-mediated preventive cardiovascular effects and discusses novel insights into the biology and mechanism of action of vitamin E metabolites in CVD. © 2019 IUBMB Life, 71(4):507-515, 2019.
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Affiliation(s)
- Erdi Sozen
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Turkey
| | - Tugce Demirel
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Turkey
| | - Nesrin Kartal Ozer
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Turkey
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Hannon BA, Khan NA, Teran-Garcia M. Nutrigenetic Contributions to Dyslipidemia: A Focus on Physiologically Relevant Pathways of Lipid and Lipoprotein Metabolism. Nutrients 2018; 10:E1404. [PMID: 30279335 PMCID: PMC6213032 DOI: 10.3390/nu10101404] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 09/19/2018] [Accepted: 09/27/2018] [Indexed: 12/11/2022] Open
Abstract
Cardiovascular disease (CVD) remains the number one cause of death worldwide, and dyslipidemia is a major predictor of CVD mortality. Elevated lipid concentrations are the result of multiple genetic and environmental factors. Over 150 genetic loci have been associated with blood lipid levels. However, not all variants are present in pathways relevant to the pathophysiology of dyslipidemia. The study of these physiologically relevant variants can provide mechanistic understanding of dyslipidemia and identify potential novel therapeutic targets. Additionally, dietary fatty acids have been evidenced to exert both positive and negative effects on lipid profiles. The metabolism of both dietary and endogenously synthesized lipids can be affected by individual genetic variation to produce elevated lipid concentrations. This review will explore the genetic, dietary, and nutrigenetic contributions to dyslipidemia.
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Affiliation(s)
- Bridget A Hannon
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL 61801, USA.
| | - Naiman A Khan
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL 61801, USA.
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL 61801, USA.
| | - Margarita Teran-Garcia
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL 61801, USA.
- Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL 61801, USA.
- Department of Human Development and Family Studies, Cooperative Extension, University of Illinois at Urbana-Champaign, Carle Illinois College of Medicine, Urbana-Champaign, IL 61801, USA.
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Son NH, Basu D, Samovski D, Pietka TA, Peche VS, Willecke F, Fang X, Yu SQ, Scerbo D, Chang HR, Sun F, Bagdasarov S, Drosatos K, Yeh ST, Mullick AE, Shoghi KI, Gumaste N, Kim K, Huggins LA, Lhakhang T, Abumrad NA, Goldberg IJ. Endothelial cell CD36 optimizes tissue fatty acid uptake. J Clin Invest 2018; 128:4329-4342. [PMID: 30047927 PMCID: PMC6159965 DOI: 10.1172/jci99315] [Citation(s) in RCA: 166] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 07/18/2018] [Indexed: 12/30/2022] Open
Abstract
Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multiligand receptor cluster of differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs and parenchymal cells such as myocytes and adipocytes. Whether tissue uptake of FAs is dependent on EC or parenchymal cell CD36, or both, is unknown. Using a cell-specific deletion approach, we show that EC, but not parenchymal cell, CD36 deletion increased fasting plasma FAs and postprandial triglycerides. EC-Cd36-KO mice had reduced uptake of radiolabeled long-chain FAs into heart, skeletal muscle, and brown adipose tissue; these uptake studies were replicated using [11C]palmitate PET scans. High-fat diet-fed EC-CD36-deficient mice had improved glucose tolerance and insulin sensitivity. Both EC and cardiomyocyte (CM) deletion of CD36 reduced heart lipid droplet accumulation after fasting, but CM deletion did not affect heart glucose or FA uptake. Expression in the heart of several genes modulating glucose metabolism and insulin action increased with EC-CD36 deletion but decreased with CM deletion. In conclusion, EC CD36 acts as a gatekeeper for parenchymal cell FA uptake, with important downstream effects on glucose utilization and insulin action.
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Affiliation(s)
- Ni-Huiping Son
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Debapriya Basu
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Dmitri Samovski
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Terri A. Pietka
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Vivek S. Peche
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Florian Willecke
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Xiang Fang
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Shui-Qing Yu
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Diego Scerbo
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Hye Rim Chang
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Fei Sun
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Svetlana Bagdasarov
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Konstantinos Drosatos
- Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Steve T. Yeh
- Ionis Pharmaceuticals Inc., Carlsbad, California, USA
| | | | - Kooresh I. Shoghi
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Namrata Gumaste
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - KyeongJin Kim
- Division of Endocrinology, Columbia University Medical Center, New York, New York, USA
| | - Lesley-Ann Huggins
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
| | - Tenzin Lhakhang
- NYU Genome Technology Center, NYU Langone Medical Center, New York, New York, USA
| | - Nada A. Abumrad
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Ira J. Goldberg
- Division of Endocrinology, Diabetes and Metabolism, New York University School of Medicine, New York, New York, USA
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Bai X, Xu C, Wen D, Chen Y, Li H, Wang X, Zhou L, Huang M, Jin J. Polymorphisms of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36) associated with valproate-induced obesity in epileptic patients. Psychopharmacology (Berl) 2018; 235:2665-2673. [PMID: 29984389 DOI: 10.1007/s00213-018-4960-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 06/26/2018] [Indexed: 12/20/2022]
Abstract
RATIONALE Valproate (VPA) is a choice for the treatment of primary generalized epilepsies and partial epilepsies. Unfortunately, weight gain or obesity is one of the most frequent adverse effects of VPA treatment. Genetic factors were shown to be involved in the effect. OBJECTIVE The aim of this study was to investigate the association of selected single nucleotide polymorphisms (SNPs) of cluster of differentiation 36 (CD36) and peroxisome proliferator-activated receptor γ (PPARγ) with VPA-induced weight gain and obesity in epileptic patients. METHODS A total of 225 Chinese Han epilepsy patients receiving VPA treatment were recruited in the study. Height and weight for the calculation of body mass index (BMI) were measured at the initiation of VPA therapy and in the follow-up examination. A BMI of 25 kg/m2 or higher was defined as obesity on the basis of the World Health Organization (WHO) criteria for Asian populations. Four SNPs in CD36 (rs1194197, rs7807607) and PPARγ (rs10865710, rs2920502) were genotyped using the Sequenom® MassArray iPlex platform. RESULTS About 19.6% of epileptic patients receiving VPA therapy were found to become obese. After covariate analysis of age, gender, sex, height, initial BMI, and VPA dosage, the CD36 rs1194197 C allele and rs7807607 T allele (OR, 0.31; 95%CI, 0.13-0.72; P = 0.009 and OR, 0.38; 95%CI; 0.18-0.83; P = 0.02, respectively) were identified as protective factors for VPA-induced obesity. The PPARγ rs10865710 C allele carriers were found to be less likely to suffer from VPA-induced obesity compared with GG genotype carriers (OR, 0.04; 95%CI, 0.01-0.12; P < 0.001). After a Bonferroni correction for multiple comparisons, the genotypic associations of CD36 rs1194197 and PPARγ rs10865710 and the allelic association of CD36 rs7807607 with obesity remained statistically significant. CONCLUSIONS Our data first indicated that CD36 and PPARγ polymorphisms may be associated with VPA-induced obesity and weight gain, suggesting that CD36 and PPARγ may have potential value in predicting VPA-induced obesity in Chinese Han epileptic patients.
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Affiliation(s)
- Xupeng Bai
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Chuncao Xu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Dingsheng Wen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Yibei Chen
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Hongliang Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Xueding Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Liemin Zhou
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
| | - Min Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
| | - Jing Jin
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
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Holmes M, Connor T, Oldmeadow C, Pockney PG, Scott RJ, Talseth-Palmer BA. CD36 - a plausible modifier of disease phenotype in familial adenomatous polyposis. Hered Cancer Clin Pract 2018; 16:14. [PMID: 30065793 PMCID: PMC6064055 DOI: 10.1186/s13053-018-0096-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 07/19/2018] [Indexed: 12/31/2022] Open
Abstract
Background Familial adenomatous polyposis (FAP) is a well characterised genetic predisposition to early onset colorectal cancer (CRC) that is characterised by polyposis of the colon and rectum. Animal models have consistently suggested the role of modifier genes in determining disease phenotype, yet none have been substantiated in the human population. The mouse homologue of cluster of differentiation 36 (CD36) has been proposed as a modifier of disease in the MIN mouse model of FAP. Methods Three single nucleotide polymorphisms (SNPs); rs1049673, rs1761667 and rs1984112 in CD36, have been investigated in 275 FAP patients to determine if they were associated with age of polyposis or risk of developing disease. Results The results revealed a substantially lower age of polyposis diagnosis for patients belonging to the severe FAP group (harbouring adenomatous polyposis coli (APC) variants in the mutation cluster region (MCR)) and high age for patients in the attenuated familial adenomatous polyposis (AFAP) group for SNPs rs1761667 and rs1984112. Conclusions This study provides evidence for patients belonging to the MCR and AFAP groups harbouring specific genotypes for SNPs in CD36 to initiate screening/treatment for FAP at much earlier (MCR) and much later (AFAP) ages than the norm in today’s clinical practice. The findings need to be verified in an independent FAP patient cohort.
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Affiliation(s)
- Merran Holmes
- 1School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW Australia.,2Department of Surgery, John Hunter Hospital, Newcastle, Australia
| | - Toni Connor
- 1School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW Australia.,Pathology North, NSW Health Pathology, Newcastle, Australia
| | - Christopher Oldmeadow
- 4Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW Australia
| | - Peter G Pockney
- 1School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW Australia.,2Department of Surgery, John Hunter Hospital, Newcastle, Australia
| | - Rodney J Scott
- Pathology North, NSW Health Pathology, Newcastle, Australia.,5School of Biomedical Science and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia
| | - Bente A Talseth-Palmer
- 5School of Biomedical Science and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.,6Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.,Clinic for Medicine, Møre og Romsdal Hospital Trust, Molde, Norway
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Maréchal L, Laviolette M, Rodrigue-Way A, Sow B, Brochu M, Caron V, Tremblay A. The CD36-PPARγ Pathway in Metabolic Disorders. Int J Mol Sci 2018; 19:1529. [PMID: 29883404 PMCID: PMC5983591 DOI: 10.3390/ijms19051529] [Citation(s) in RCA: 114] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 05/08/2018] [Accepted: 05/16/2018] [Indexed: 12/21/2022] Open
Abstract
Uncovering the biological role of nuclear receptor peroxisome proliferator-activated receptors (PPARs) has greatly advanced our knowledge of the transcriptional control of glucose and energy metabolism. As such, pharmacological activation of PPARγ has emerged as an efficient approach for treating metabolic disorders with the current use of thiazolidinediones to improve insulin resistance in diabetic patients. The recent identification of growth hormone releasing peptides (GHRP) as potent inducers of PPARγ through activation of the scavenger receptor CD36 has defined a novel alternative to regulate essential aspects of lipid and energy metabolism. Recent advances on the emerging role of CD36 and GHRP hexarelin in regulating PPARγ downstream actions with benefits on atherosclerosis, hepatic cholesterol biosynthesis and fat mitochondrial biogenesis are summarized here. The response of PPARγ coactivator PGC-1 is also discussed in these effects. The identification of the GHRP-CD36-PPARγ pathway in controlling various tissue metabolic functions provides an interesting option for metabolic disorders.
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Affiliation(s)
- Loïze Maréchal
- Research Center, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada.
- Department of Physiology, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada.
| | - Maximilien Laviolette
- Research Center, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada.
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada.
| | - Amélie Rodrigue-Way
- Research Center, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada.
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada.
| | - Baly Sow
- Research Center, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada.
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada.
| | - Michèle Brochu
- Department of Physiology, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada.
| | - Véronique Caron
- Research Center, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada.
| | - André Tremblay
- Research Center, CHU Sainte-Justine, Montréal, QC H3T 1C5, Canada.
- Department of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1J4, Canada.
- Centre de Recherche en Reproduction et Fertilité, University of Montreal, Saint Hyacinthe, QC J2S 7C6, Canada.
- Department of Obstetrics & Gynecology, Faculty of Medicine, University of Montreal, Montréal, QC H3T 1C5, Canada.
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Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial. EBioMedicine 2018; 31:150-156. [PMID: 29703528 PMCID: PMC6013782 DOI: 10.1016/j.ebiom.2018.04.012] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 04/13/2018] [Accepted: 04/13/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear. METHODS In a double-blind randomized controlled trial, 150 patients with type 2 diabetes (T2D) were randomized into omega-3 fatty acid group (n = 56 for fish oil and 44 for flaxseed oil) and control group (n = 50) for 180 days. All patients were genotyped for genetic variants at CD36 (rs1527483), NOS3 (rs1799983) and PPARG (rs1801282). Linear regression was used to examine the interaction between omega-3 fatty acid intervention and CD36, NOS3 or PPARG variants for blood lipids. FINDINGS Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (p-interaction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). We also found a significant interaction between change in erythrocyte phospholipid omega-3 fatty acid composition and NOS3 genotype on triglycerides (p-interaction = 0.042), total cholesterol (p-interaction = 0.013) and ratio of total cholesterol to high-density lipoprotein cholesterol (p-interaction = 0.015). The T2D patients of CD36-G allele, PPARG-G allele and NOS3-A allele tended to respond better to omega-3 fatty acids in improving lipid profiles. The interaction results of the omega-3 fatty acid group were mainly attributed to the fish oil supplements. INTERPRETATION This study suggests that T2D patients with different genotypes at CD36, NOS3 and PPARG respond differentially to intervention of omega-3 supplements in blood lipid profiles.
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Cifarelli V, Abumrad NA. Intestinal CD36 and Other Key Proteins of Lipid Utilization: Role in Absorption and Gut Homeostasis. Compr Physiol 2018; 8:493-507. [PMID: 29687890 PMCID: PMC6247794 DOI: 10.1002/cphy.c170026] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Several proteins have been implicated in fatty acid (FA) transport by enterocytes including the scavenger receptor CD36 (SR-B2), the scavenger receptor B1 (SR-B1) a member of the CD36 family and the FA transport protein 4 (FATP4). Here, we review the regulation of enterocyte FA uptake and its function in lipid absorption including prechylomicron formation, assembly and transport. Emphasis is given to CD36, which is abundantly expressed along the digestive tract of rodents and humans and has been the most studied. We also address the pleiotropic functions of CD36 that go beyond lipid absorption and metabolism to include recent evidence of its impact on intestinal homeostasis and barrier maintenance. Areas of progress involving contribution of membrane phospholipid remodeling and of cytosolic FA-binding proteins, FABP1 and FABP2 to fat absorption will be covered. © 2018 American Physiological Society. Compr Physiol 8:493-507, 2018.
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Affiliation(s)
- Vincenza Cifarelli
- Department of Internal Medicine, Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri, USA
| | - Nada A. Abumrad
- Department of Internal Medicine, Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri, USA
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Rać ME, Safranow K, Garanty-Bogacka B, Dziedziejko V, Kurzawski G, Goschorska M, Kuligowska A, Pauli N, Chlubek D. CD36 gene polymorphism and plasma sCD36 as the risk factor in higher cholesterolemia. Arch Pediatr 2018; 25:177-181. [PMID: 29576254 DOI: 10.1016/j.arcped.2018.01.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 11/26/2017] [Accepted: 01/28/2018] [Indexed: 10/17/2022]
Abstract
INTRODUCTION The receptor CD36 has been reported to play an important role in atherogenicity. The aim of this study was to gain insight into the relationship between CD36 gene polymorphisms or the plasma concentration of sCD36 and clinical or biochemical parameters in children. PATIENTS AND METHODS The study groups comprised Caucasian children with and without hypercholesterolemia. The alterations in the CD36 gene were detected by DHPLC and the plasma concentrations of sCD36 were measured by ELISA. RESULTS The data presented suggest that the IVS4-10A allele of CD36 (rs3211892) is associated with a lower risk of hypercholesterolemia. We observed a negative correlation of the sCD36 concentration with uric acid and insulin concentrations, the HOMA-IR ratio, weight, waist and hip circumference, systolic blood pressure, body mass index, waist-hip ratio and mean arterial pressure ratio, but a positive correlation with HDL cholesterol and ApoA1 concentrations. Female gender was a significant independent predictor of a higher plasma sCD36 concentration. CONCLUSIONS The data presented suggest a possible protective effect of a higher sCD36 concentration in relation to metabolic syndrome components.
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Affiliation(s)
- M E Rać
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland.
| | - K Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - B Garanty-Bogacka
- Independent Laboratory of Propedeutics in Pediatrics, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland
| | - V Dziedziejko
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - G Kurzawski
- Department of Genetics and Pathomorphology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - M Goschorska
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - A Kuligowska
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - N Pauli
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - D Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
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Melis M, Mastinu M, Arca M, Crnjar R, Tomassini Barbarossa I. Effect of chemical interaction between oleic acid and L-Arginine on oral perception, as a function of polymorphisms of CD36 and OBPIIa and genetic ability to taste 6-n-propylthiouracil. PLoS One 2018; 13:e0194953. [PMID: 29566052 PMCID: PMC5864069 DOI: 10.1371/journal.pone.0194953] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Accepted: 03/13/2018] [Indexed: 01/22/2023] Open
Abstract
Oral sensitivity to fats varies in individuals influencing nutritional status and health. Variations in oleic acid perception are associated with CD36 and odorant binding protein (OBPIIa) polymorphisms, and 6-n-propylthiouracil (PROP) sensitivity, which is mediated by TAS2R38 receptor. L-Arginine (L-Arg) supplementation was shown to modify the perception of the five taste qualities. Here we analyzed the effect of three concentrations (5, 10, 15 mmol/L) of L-Arg on oral perception of oleic acid in forty-six subjects classified for PROP taster status and genotyped for TAS2R38, CD36 and OBPIIa polymorphisms. L-Arg supplementation was effective in increasing the perceived intensity of oleic acid in most subjects. The lowest concentration was the most effective, especially in PROP non-tasters or medium tasters, and in subjects with at least an allele A in CD36 and OBPIIa loci. Density Functional Theory (DFT) calculations were exploited to characterize the chemical interaction between L-Arg and oleic acid, showing that a stable 1:1 oleate·ArgH+ adduct can be formed, stabilized by a pair of hydrogen bonds. Results indicate that L-Arg, acting as a ‘carrier’ of fatty acids in saliva, can selectively modify taste response, and suggest that it may to be used in personalized dietetic strategies to optimize eating behaviors and health.
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Affiliation(s)
- Melania Melis
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy
| | - Mariano Mastinu
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy
| | - Massimiliano Arca
- Department of Chemical and Geological Sciences, University of Cagliari, Monserrato, CA, Italy
| | - Roberto Crnjar
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy
| | - Iole Tomassini Barbarossa
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy
- * E-mail:
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Zhang D, Zhang R, Liu Y, Sun X, Yin Z, Li H, Zhao Y, Wang B, Ren Y, Cheng C, Liu X, Liu D, Liu F, Chen X, Liu L, Zhou Q, Xiong Y, Xu Q, Liu J, Hong S, You Z, Hu D, Zhang M. CD36 gene variants is associated with type 2 diabetes mellitus through the interaction of obesity in rural Chinese adults. Gene 2018; 659:155-159. [PMID: 29572193 DOI: 10.1016/j.gene.2018.03.060] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 03/14/2018] [Accepted: 03/19/2018] [Indexed: 01/08/2023]
Abstract
BACKGROUND Evidences show that cluster determinant 36 (CD36) protein plays a role in lipid metabolism and insulin resistance, and the expression of CD36 is inducible in obesity. The present study evaluated the association of CD36 variants and the interaction with obesity on type 2 diabetes mellitus (T2DM) risk. METHODS We performed a case-control study nested in the Rural Chinese Cohort Study. We included 546 incident T2DM cases matched with non-T2DM controls in a 1:1 ratio by sex, age (within 2 years), marital status, and residence village. Four loci in CD36 (rs1194197, rs2151916, rs3211956, and rs7755) were genotyped by SNPscanTM Genotyping system. RESULTS After adjusting for potential confounding, we observed no statistically significant association between the CD36 polymorphisms and T2DM risk. Compared to wild-type homozygous carriers with normal weight, overweight/obesity participants carrying the mutational allele rs7755 showed increased risk of T2DM, by 114% (OR = 2.14, 95% CI: 1.33-3.46; Pinteraction = 0.007); abdominal obesity participants carrying the mutational allele rs7755 showed increased risk of T2DM, by 133% (OR = 2.33, 95% CI: 1.48-3.66; Pinteraction = 0.002). Furthermore, rs2151916 polymorphism was associated with triglycerides level (P = 0.019), and the rs1194197 variant was related to systolic blood pressure (P = 0.023) within the group of controls. CONCLUSIONS CD36 genotypes were not associated with the progression to T2DM independently. However, our results suggested a positive interaction between the CD36 variants and obesity on T2DM susceptibility, which might be through a cardiometabolic disorder.
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Affiliation(s)
- Dongdong Zhang
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Ruiyuan Zhang
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yu Liu
- The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Xizhuo Sun
- The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Zhaoxia Yin
- The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Honghui Li
- The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Zhao
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Bingyuan Wang
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yongcheng Ren
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Cheng Cheng
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Xuejiao Liu
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Dechen Liu
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Feiyan Liu
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Xu Chen
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Leilei Liu
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Qionggui Zhou
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yihan Xiong
- Department of Clinical Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Qihuan Xu
- Department of Clinical Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Jiali Liu
- Department of Clinical Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Shihao Hong
- Department of Clinical Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Ziyang You
- Department of Clinical Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Dongsheng Hu
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Ming Zhang
- Department of Preventive Medicine, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.
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The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid detection and obesity in Czech young adults. Br J Nutr 2018; 119:472-478. [DOI: 10.1017/s0007114517003981] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AbstractRecent evidence has raised the possibility of the existence of a sixth taste modality – that is, taste for fat – which is mediated by lingual CD36 and plays a role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to be associated with altered oro-sensory detection of dietary lipids. In the present study, we investigated the relationship between oro-sensory perception of linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity parameters and craving habits for dietary lipids in young Czech adults. We also sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be responsible for the difference in taste perception. We observed that craving for dietary lipids was correlated with anthropometric parameters (P<0·05) and LA detection threshold (P=0·033). The participants with the CC genotype of the rs1527483 polymorphism had lower BMI (P=0·011), waist circumference (P=0·005), waist:height ratio (P=0·010) and higher sensitivity for LA (P=0·037) than the participants with the CT and TT genotypes. Interestingly, we did not observe any association between the rs3212018 polymorphism and the studied parameters. Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in these subjects. Finally, we can state that rs1527483, but not rs3212018, is associated with high body weight in young Czech subjects.
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Abstract
The hydrophobicity of vitamin E poses transport and metabolic challenges to regulate its bioavailability and to prevent its accumulation in lipid-rich tissues such as adipose tissue, brain, and liver. Water-soluble precursors of vitamin E (α-tocopherol, αT), such as its esters with acetate (αTA), succinate (αTS), or phosphate (αTP), have increased solubility in water and stability against reaction with free radicals, but they are rapidly converted during their uptake into the lipid-soluble vitamin E. Therefore, the bioavailability of these precursors as intact molecules is low; nevertheless, at least for αTS and αTP, the recent research has revealed unique regulatory effects on signal transduction and gene expression and the modulation of cellular events ranging from proliferation, survival/apoptosis, lipid uptake and metabolism, phagocytosis, long term potentiation, cell migration, telomere maintenance, and angiogenesis. Moreover, water-soluble derivatives of vitamin E including some based on αTP are increasingly used as components of nanocarriers for enhanced and targeted delivery of drugs and other molecules (vitamins, including αT and αTP itself, vitamin D3, carnosine, caffeine, docosahexaenoic acid (DHA), insulin) and cofactors such as coenzyme Q10. In this review, the chemical characteristics, transport, metabolic pathways, and molecular mechanisms of action of αTP in cells and tissues are summarized and put into perspective with its possible role in the prevention of a number of diseases.
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Affiliation(s)
- Jean-Marc Zingg
- Miller School of Medicine, University of Miami, Miami, FL, United States.
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Sihag J, Jones PJH. Oleoylethanolamide: The role of a bioactive lipid amide in modulating eating behaviour. Obes Rev 2018; 19:178-197. [PMID: 29124885 DOI: 10.1111/obr.12630] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 09/19/2017] [Accepted: 09/19/2017] [Indexed: 12/13/2022]
Abstract
Fatty acid ethanolamides are lipid mediators that regulate a plethora of physiological functions. One such bioactive lipid mediator, oleoylethanolamide (OEA), is a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR-α), which modulates increased expression of the fatty acid translocase CD36 that enables the regulation of feeding behaviour. Consumption of dietary fat rich in oleic acid activates taste receptors in the gut activating specific enzymes that lead to the formation of OEA. OEA further combines with PPAR-α to enable fat oxidation in the liver, resulting in enhanced energy production. Evidence suggests that sustained ingestion of a high-fat diet abolishes the anorexic signal of OEA. Additionally, malfunction of the enterocyte that transforms oleic acid produced during fat digestion into OEA might be responsible for reduced satiety and hyperphagia, resulting in overweight and obesity. Thus, OEA anorectic signalling may be an essential element of the physiology and metabolic system regulating dietary fat intake and obesity. The evidence reviewed in this article indicates that intake of oleic acid, and thereby the resulting OEA imparting anorexic properties, is dependent on CD36, PPAR-α, enterocyte fat sensory receptors, histamine, oxytocin and dopamine; leading to increased fat oxidation and enhanced energy expenditure to induce satiety and increase feeding latency; and that a disruption in any of these systems will cease/curb fat-induced satiety.
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Affiliation(s)
- J Sihag
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.,Richardson Centre for Functional Foods and Nutraceuticals (RCFFN), University of Manitoba, Winnipeg, Manitoba, Canada
| | - P J H Jones
- Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.,Richardson Centre for Functional Foods and Nutraceuticals (RCFFN), University of Manitoba, Winnipeg, Manitoba, Canada
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Melis M, Carta G, Pintus S, Pintus P, Piras CA, Murru E, Manca C, Di Marzo V, Banni S, Tomassini Barbarossa I. Polymorphism rs1761667 in the CD36 Gene Is Associated to Changes in Fatty Acid Metabolism and Circulating Endocannabinoid Levels Distinctively in Normal Weight and Obese Subjects. Front Physiol 2017; 8:1006. [PMID: 29270130 PMCID: PMC5724198 DOI: 10.3389/fphys.2017.01006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 11/21/2017] [Indexed: 12/25/2022] Open
Abstract
The multifunctional CD36 scavenger receptor facilitates fatty acid (FA) uptake and oxidation and it has been involved in the pathophysiology related to dysfunctional FA metabolism. The common variant in the CD36 gene, rs1761667 (A/G), whose allele A is characterized by a reduced protein expression, has been associated with taste sensitivity to and preference for fat. We therefore aimed at evaluating whether the CD36 polymorphism may influence fatty acid metabolism and endocannabinoid biosynthesis in normal weight (NW) and obese (OB) subjects. Red blood cell (RBC) fatty acid composition, and plasma endocannabinoid levels were determined. In NW subjects with AA genotype was found a marked reduction of RBC saturated fatty acids and palmitic/linoleic ratio (PA/LA), considered as de novo lipogenesis (DNL) biomarkers. Remarkably, to the reduction of DNL biomarkers corresponded an increase of omega-6 index, an indirect marker of the impact on fatty acid metabolism of dietary omega-6 fatty acids, endocannabinoid levels and a higher waist/hip ratio. The presence of the G allele was instead associated with increased endocannabinoid plasma levels and a trend for increased waist/hip ratio in obese subjects, even though exhibited decreased BMI with respect to those with AA genotype. These data indicate that the CD36 polymorphism, rs1761667, leads to a distinct metabolic pattern in NW and in OB subjects. Therefore, their determination may be crucial in developing personalized therapeutic strategies for ameliorating dyslipidemia and other metabolic disorders.
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Affiliation(s)
- Melania Melis
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, Italy
| | - Gianfranca Carta
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, Italy
| | - Stefano Pintus
- Department of Internal Medicine, Center for Metabolic Diseases, Azienda Ospedaliera G. Brotzu, Cagliari, Italy
| | - Paolo Pintus
- Department of Internal Medicine, Center for Metabolic Diseases, Azienda Ospedaliera G. Brotzu, Cagliari, Italy
| | - Carla A Piras
- Department of Internal Medicine, Center for Metabolic Diseases, Azienda Ospedaliera G. Brotzu, Cagliari, Italy
| | - Elisabetta Murru
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, Italy
| | - Claudia Manca
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, Italy
| | - Vincenzo Di Marzo
- Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy
| | - Sebastiano Banni
- Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, Italy
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CD36 in chronic kidney disease: novel insights and therapeutic opportunities. Nat Rev Nephrol 2017; 13:769-781. [DOI: 10.1038/nrneph.2017.126] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Chamoun E, Mutch DM, Allen-Vercoe E, Buchholz AC, Duncan AM, Spriet LL, Haines J, Ma DWL. A review of the associations between single nucleotide polymorphisms in taste receptors, eating behaviors, and health. Crit Rev Food Sci Nutr 2017; 58:194-207. [DOI: 10.1080/10408398.2016.1152229] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Pioltine MB, de Melo ME, Santos A, Machado AD, Fernandes AE, Fujiwara CT, Cercato C, Mancini MC. Genetic Variation in CD36 Is Associated with Decreased Fat and Sugar Intake in Obese Children and Adolescents. JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS 2017; 9:300-305. [DOI: 10.1159/000455915] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 01/10/2017] [Indexed: 12/14/2022]
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Ong HH, Tan YN, Say YH. Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects. Physiol Behav 2017; 168:128-137. [DOI: 10.1016/j.physbeh.2016.11.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 10/03/2016] [Accepted: 11/10/2016] [Indexed: 01/07/2023]
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