|
1
|
FINK JULIUS, TANAKA MASAMI, HORIE SHIGEO. Effects of Fasting on Metabolic Hormones and Functions: A Narrative Review. JUNTENDO IJI ZASSHI = JUNTENDO MEDICAL JOURNAL 2024; 70:348-359. [PMID: 39545228 PMCID: PMC11560338 DOI: 10.14789/jmj.jmj24-0012-r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 06/17/2024] [Indexed: 11/17/2024]
Abstract
The occurrence of the metabolic syndrome and its related diseases such as diabetes are steadily rising in our modern society. Modern food choices and the more sedentary lifestyles largely contribute to this shift in our society's health. Fasting has been practiced for religious purposes all over the world long time before science showed the benefits of it. The effects of fasting on glucose and fat metabolism are of great interest. Fasting triggers a cascade of changes in the hormonal, microbiome and enzymatic environments, leading to shifted glucose and fat metabolisms. Fasting-induced metabolic function changes are affected by several factors such as sex hormones, lipid-released hormones, growth hormone, insulin, and the gut microbiome, leading to lipolysis and the release of FFA into the bloodstream. The purpose of this review is to summarize the newest research results on the specific pathways fasting triggers to improve metabolic functions and understand the potential applications of fasting as prevention/treatment of several metabolic conditions.
Collapse
Affiliation(s)
- JULIUS FINK
- Corresponding author: Julius Fink, Department of Urology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan, TEL: +81-3-3813-3111 E-mail:
| | | | | |
Collapse
|
|
2
|
Min SH, Song DK, Lee CH, Roh E, Kim MS. Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator. Endocrinol Metab (Seoul) 2024; 39:1-11. [PMID: 38356211 PMCID: PMC10901667 DOI: 10.3803/enm.2024.1922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 01/05/2024] [Accepted: 01/09/2024] [Indexed: 02/16/2024] Open
Abstract
5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps cells maintain stable energy levels during metabolic stress. The hypothalamus is pivotal in regulating energy balance within the body. Certain neurons in the hypothalamus are sensitive to fluctuations in food availability and energy stores, triggering adaptive responses to preserve systemic energy equilibrium. AMPK, expressed in these hypothalamic neurons, is instrumental in these regulatory processes. Hypothalamic AMPK activity is modulated by key metabolic hormones. Anorexigenic hormones, including leptin, insulin, and glucagon-like peptide 1, suppress hypothalamic AMPK activity, whereas the hunger hormone ghrelin activates it. These hormonal influences on hypothalamic AMPK activity are central to their roles in controlling food consumption and energy expenditure. Additionally, hypothalamic AMPK activity responds to variations in glucose concentrations. It becomes active during hypoglycemia but is deactivated when glucose is introduced directly into the hypothalamus. These shifts in AMPK activity within hypothalamic neurons are critical for maintaining glucose balance. Considering the vital function of hypothalamic AMPK in the regulation of overall energy and glucose balance, developing chemical agents that target the hypothalamus to modulate AMPK activity presents a promising therapeutic approach for metabolic conditions such as obesity and type 2 diabetes mellitus.
Collapse
Affiliation(s)
- Se Hee Min
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Diabetes Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Kyeong Song
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Chan Hee Lee
- Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon, Korea
| | - Eun Roh
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Korea
| | - Min-Seon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Diabetes Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
3
|
Shin J, Toyoda S, Nishitani S, Fukuhara A, Kita S, Otsuki M, Shimomura I. Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19. Diabetes 2021; 70:2745-2755. [PMID: 34615619 PMCID: PMC8660985 DOI: 10.2337/db20-1094] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 09/29/2021] [Indexed: 12/20/2022]
Abstract
Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium-glucose cotransporter 2 inhibitor, or β3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.
Collapse
Affiliation(s)
- Jihoon Shin
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Shinichiro Toyoda
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Shigeki Nishitani
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Atsunori Fukuhara
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Adipose Management, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Shunbun Kita
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Adipose Management, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Michio Otsuki
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| |
Collapse
|
|
4
|
Suleiman N, Alkasem M, Hassoun S, Abdalhakam I, Bettahi I, Mir F, Ramanjaneya M, Jerobin J, Iskandarani A, Samra TA, Chandra P, Skarulis M, Abou-Samra AB. Insulin sensitivity variations in apparently healthy Arab male subjects: correlation with insulin and C peptide. BMJ Open Diabetes Res Care 2021; 9:9/2/e002039. [PMID: 34785564 PMCID: PMC8596034 DOI: 10.1136/bmjdrc-2020-002039] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 06/30/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Decreased insulin sensitivity occurs early in type 2 diabetes (T2D). T2D is highly prevalent in the Middle East and North Africa regions. This study assessed the variations in insulin sensitivity in normal apparently healthy subjects and the levels of adiponectin, adipsin and inflammatory markers. RESEARCH DESIGN AND METHODS A total of 60 participants (aged 18-45, body mass index <28) with a normal oral glucose tolerance test (OGTT) completed hyperinsulinemic-euglycemic clamp (40 mU/m2/min) and body composition test by dual-energy X-ray absorptiometry scan. Blood samples were assayed for glucose, insulin, C peptide, inflammatory markers, oxidative stress markers, adiponectin and adipsin. RESULTS The subjects showed wide variations in the whole-body glucose disposal rate (M value) from 2 to 20 mg/kg/min and were divided into three groups: most responsive (M>12 mg/kg/min, n=17), least responsive (M≤6 mg/kg/min, n=14) and intermediate responsive (M=6.1-12 mg/kg/min, n=29). Insulin and C peptide responses to OGTT were highest among the least insulin sensitive group. Triglycerides, cholesterol, alanine transaminase (ALT) and albumin levels were higher in the least responsive group compared with the other groups. Among the inflammatory markers, C reactive protein (CRP) was highest in the least sensitivity group compared with the other groups; however, there were no differences in the level of soluble receptor for advanced glycation end products and Tumor Necrosis Factor Receptor Superfamily 1B (TNFRS1B). Plasma levels of insulin sensitivity markers, adiponectin and adipsin, and oxidative stress markers, oxidized low-density lipoprotein, total antioxidant capacity and glutathione peroxidase 1, were similar between the groups. CONCLUSIONS A wide range in insulin sensitivity and significant differences in triglycerides, cholesterol, ALT and CRP concentrations were observed despite the fact that the study subjects were homogenous in terms of age, gender and ethnic background, and all had normal screening comprehensive chemistry and normal glucose response to OGTT. The striking differences in insulin sensitivity reflect differences in genetic predisposition and/or environmental exposure. The low insulin sensitivity status associated with increased insulin level may represent an early stage of metabolic abnormality.
Collapse
Affiliation(s)
- Noor Suleiman
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | - Meis Alkasem
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | - Shaimaa Hassoun
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | | | - Ilham Bettahi
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Fayaz Mir
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Manjunath Ramanjaneya
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Jayakumar Jerobin
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Ahmad Iskandarani
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Tareq A Samra
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Prem Chandra
- Medical Research Center, Hamad Medical Corporation, Doha, Qatar
| | - Monica Skarulis
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | | |
Collapse
|
|
5
|
Nielsen MB, Çolak Y, Benn M, Nordestgaard BG. Low Plasma Adiponectin in Risk of Type 2 Diabetes: Observational Analysis and One- and Two-Sample Mendelian Randomization Analyses in 756,219 Individuals. Diabetes 2021; 70:2694-2705. [PMID: 34426507 DOI: 10.2337/db21-0131] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022]
Abstract
We tested the hypothesis that low plasma adiponectin is associated observationally and causally with increased risk of type 2 diabetes. Observational analyses are prone to confounding and reverse causation, while genetic Mendelian randomization (MR) analyses are much less influenced by these biases. We examined 30,045 individuals from the Copenhagen General Population Study observationally (plasma adiponectin [1,751 individuals with type 2 diabetes]), 96,903 Copenhagen individuals using one-sample MR (5 genetic variants [5,012 individuals with type 2 diabetes]), and 659,316 Europeans (ADIPOGen, GERA, DIAGRAM, UK Biobank) using two-sample MR (10 genetic variants [62,892 individuals type 2 diabetes]). Observationally, and in comparisons with individuals with median plasma adiponectin of 28.9 μg/mL (4th quartile), multivariable adjusted hazard ratios (HRs) for type 2 diabetes were 1.42 (95% CI 1.18-1.72) for 19.2 μg/mL (3rd quartile), 2.21 (1.84-2.66) for 13.9 μg/mL (2nd quartile), and 4.05 (3.38-4.86) for 9.2 μg/mL (1st quartile). Corresponding cumulative incidence for type 2 diabetes at age 70 years was 3%, 7%, 11%, and 20%, respectively. A 1 μg/mL lower plasma adiponectin conferred an HR for type 2 diabetes of 1.07 (1.06-1.09), while genetic, causal risk ratio per 1 unit log-transformed lower plasma adiponectin was 1.13 (95% CI 0.83-1.53) in one-sample MR and 1.26 (1.01-1.57) in two-sample MR. In conclusion, low plasma adiponectin is associated with increased risk of type 2 diabetes, an association that could represent a causal relationship.
Collapse
Affiliation(s)
- Maria B Nielsen
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Yunus Çolak
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Section of Respiratory Medicine, Department of Internal Medicine, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
| | - Marianne Benn
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
|
6
|
Yong J, Parekh VS, Reilly SM, Nayak J, Chen Z, Lebeaupin C, Jang I, Zhang J, Prakash TP, Sun H, Murray S, Guo S, Ayala JE, Satin LS, Saltiel AR, Kaufman RJ. Chop/ Ddit3 depletion in β cells alleviates ER stress and corrects hepatic steatosis in mice. Sci Transl Med 2021; 13:13/604/eaba9796. [PMID: 34321322 DOI: 10.1126/scitranslmed.aba9796] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 04/07/2021] [Accepted: 06/23/2021] [Indexed: 12/21/2022]
Abstract
Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia, hyperinsulinemia, and insulin resistance (IR). During the early phase of T2D, insulin synthesis and secretion by pancreatic β cells is enhanced, which can lead to proinsulin misfolding that aggravates endoplasmic reticulum (ER) protein homeostasis in β cells. Moreover, increased circulating insulin may contribute to fatty liver disease. Medical interventions aimed at alleviating ER stress in β cells while maintaining optimal insulin secretion are therefore an attractive therapeutic strategy for T2D. Previously, we demonstrated that germline Chop gene deletion preserved β cells in high-fat diet (HFD)-fed mice and in leptin receptor-deficient db/db mice. In the current study, we further investigated whether targeting Chop/Ddit3 specifically in murine β cells conferred therapeutic benefits. First, we showed that Chop deletion in β cells alleviated β cell ER stress and delayed glucose-stimulated insulin secretion (GSIS) in HFD-fed mice. Second, β cell-specific Chop deletion prevented liver steatosis and hepatomegaly in aged HFD-fed mice without affecting basal glucose homeostasis. Third, we provide mechanistic evidence that Chop depletion reduces ER Ca2+ buffering capacity and modulates glucose-induced islet Ca2+ oscillations, leading to transcriptional changes of ER chaperone profile ("ER remodeling"). Last, we demonstrated that a GLP1-conjugated Chop antisense oligonucleotide strategy recapitulated the reduction in liver triglycerides and pancreatic insulin content. In summary, our results demonstrate that Chop depletion in β cells provides a therapeutic strategy to alleviate dysregulated insulin secretion and consequent fatty liver disease in T2D.
Collapse
Affiliation(s)
- Jing Yong
- Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA. .,Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA
| | - Vishal S Parekh
- Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.,Department of Pharmacology, University of Michigan Medical School, 1000 Wall St., Ann Arbor, MI 48105, USA
| | - Shannon M Reilly
- Department of Pharmacology, University of Michigan Medical School, 1000 Wall St., Ann Arbor, MI 48105, USA.,Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Jonamani Nayak
- Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.,Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA
| | - Zhouji Chen
- Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.,Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA
| | - Cynthia Lebeaupin
- Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.,Department of Pharmacology, University of Michigan Medical School, 1000 Wall St., Ann Arbor, MI 48105, USA.,Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.,Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Insook Jang
- Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.,Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA
| | - Jiangwei Zhang
- Cardiometabolic Phenotyping Core, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA.,Department of Antisense Drug Discovery, Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA
| | - Thazha P Prakash
- Cardiometabolic Phenotyping Core, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA.,Department of Antisense Drug Discovery, Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA
| | - Hong Sun
- Cardiometabolic Phenotyping Core, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA.,Department of Antisense Drug Discovery, Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA
| | - Sue Murray
- Cardiometabolic Phenotyping Core, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA.,Department of Antisense Drug Discovery, Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA
| | - Shuling Guo
- Cardiometabolic Phenotyping Core, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA.,Department of Antisense Drug Discovery, Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA
| | - Julio E Ayala
- Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.,Cardiometabolic Phenotyping Core, Sanford-Burnham Medical Research Institute, 6400 Sanger Road, Orlando, FL 32827, USA.,Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Leslie S Satin
- Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.,Department of Pharmacology, University of Michigan Medical School, 1000 Wall St., Ann Arbor, MI 48105, USA
| | - Alan R Saltiel
- Department of Pharmacology, University of Michigan Medical School, 1000 Wall St., Ann Arbor, MI 48105, USA.,Division of Metabolism and Endocrinology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.,Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA
| | - Randal J Kaufman
- Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
| |
Collapse
|
|
7
|
Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice. Proc Natl Acad Sci U S A 2020; 117:32584-32593. [PMID: 33293421 PMCID: PMC7768680 DOI: 10.1073/pnas.1922169117] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Adiponectin has emerged as a potential therapy for type 2 diabetes mellitus, but the molecular mechanism by which adiponectin reverses insulin resistance remains unclear. Two weeks of globular adiponectin (gAcrp30) treatment reduced fasting plasma glucose, triglyceride (TAG), and insulin concentrations and reversed whole-body insulin resistance, which could be attributed to both improved insulin-mediated suppression of endogenous glucose production and increased insulin-stimulated glucose uptake in muscle and adipose tissues. These improvements in liver and muscle sensitivity were associated with ∼50% reductions in liver and muscle TAG and plasma membrane (PM)-associated diacylglycerol (DAG) content and occurred independent of reductions in total ceramide content. Reductions of PM DAG content in liver and skeletal muscle were associated with reduced PKCε translocation in liver and reduced PKCθ and PKCε translocation in skeletal muscle resulting in increased insulin-stimulated insulin receptor tyrosine1162 phosphorylation, IRS-1/IRS-2-associated PI3-kinase activity, and Akt-serine phosphorylation. Both gAcrp30 and full-length adiponectin (Acrp30) treatment increased eNOS/AMPK activation in muscle and muscle fatty acid oxidation. gAcrp30 and Acrp30 infusions also increased TAG uptake in epididymal white adipose tissue (eWAT), which could be attributed to increased lipoprotein lipase (LPL) activity. These data suggest that adiponectin and adiponectin-related molecules reverse lipid-induced liver and muscle insulin resistance by reducing ectopic lipid storage in these organs, resulting in decreased plasma membrane sn-1,2-DAG-induced nPKC activity and increased insulin signaling. Adiponectin mediates these effects by both promoting the storage of TAG in eWAT likely through stimulation of LPL as well as by stimulation of AMPK in muscle resulting in increased muscle fat oxidation.
Collapse
|
|
8
|
Ho HCH, Maddaloni E, Buzzetti R. Risk factors and predictive biomarkers of early cardiovascular disease in obese youth. Diabetes Metab Res Rev 2019; 35:e3134. [PMID: 30706683 DOI: 10.1002/dmrr.3134] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 01/26/2019] [Accepted: 01/29/2019] [Indexed: 12/20/2022]
Abstract
Obesity in childhood and adolescence continues to be a major health issue due to significant health implications and to the economic burden that arise from treating this disease and its complications. Current data show that childhood obesity is no longer just a concern for developed countries, but more significantly affecting developing countries. In adult population, cardiovascular disease is the main cause of mortality and morbidity among obese patients. It is therefore believed that risk factors found in adult patients could also be observed in obese youth. These risk factors will then persist and become progressively worse if obese youth remain obese as they reach adulthood. However, risk reduction is achievable through various prevention and management strategies of obesity and obese children who become nonobese in adulthood have a significant reduction in their risk of developing cardiovascular disease. New biomarkers to improve risk assessment in obese youth are an open research field, which will eventually lead to a more targeted approach in prevention and treatment. Nevertheless, there is still a need for continuous research in understanding the roles of these biomarkers and their potential in risk prediction. Cardiovascular risk modification of childhood obesity depends on a more concerted effort among the various parties involved and particularly a global collaboration to stop the rising prevalence of the epidemic in developing countries.
Collapse
Affiliation(s)
- Howard Chong Huat Ho
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Ernesto Maddaloni
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Raffaella Buzzetti
- Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
| |
Collapse
|
|
9
|
Szrejder M, Piwkowska A. AMPK signalling: Implications for podocyte biology in diabetic nephropathy. Biol Cell 2019; 111:109-120. [DOI: 10.1111/boc.201800077] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/26/2019] [Accepted: 01/28/2019] [Indexed: 12/21/2022]
Affiliation(s)
- Maria Szrejder
- Mossakowski Medical Research Centre Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology Gdańsk Poland
| | - Agnieszka Piwkowska
- Mossakowski Medical Research Centre Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology Gdańsk Poland
| |
Collapse
|
|
10
|
Stress during Lactation Induces Insulin Resistance Associated with an Increase in Type 1 Cannabinoid Receptors in Liver and Adipose Tissue. J Nutr Metab 2019; 2019:2806519. [PMID: 30800481 PMCID: PMC6360041 DOI: 10.1155/2019/2806519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 11/19/2018] [Accepted: 11/28/2018] [Indexed: 11/23/2022] Open
Abstract
Several reports have shown that stress during lactation causes long-term metabolic and hormonal disruptions. In this study, we designed experiments to evaluate the effects of stress during lactation on the abundance of Type 1 cannabinoid/endocannabinoid receptors (CB1R) in epididymal fat and liver and development of insulin resistance in adult mice. During the whole lactation, male mice pups were daily subcutaneously injected (days 1–21) with a saline solution to produce a soft nociceptive stress (NS). Mice body weight and food intake were periodically evaluated. Adult animals were subsequently subjected to an insulin tolerance test and some days later sacrificed to evaluate the amount of epididymal fat and abundance of CB1R and adipophilin in liver and epididymal adipose tissue. Lipoprotein lipase (LPL) activity and circulating levels of leptin, adiponectin, and corticosterone were also evaluated. In this model, NS during lactation significantly increased the amount of epididymal fat and induced insulin resistance in adult mice. In addition, a significantly increased abundance of CB1R and adipophilin in epididymal fat and liver was observed, together with elevated circulating levels of leptin and corticosterone. Adult NS animals also had low plasmatic adiponectin and, although nonsignificant, had a sustained trend to a greater LPL activity associated with epididymal fat. These results indicate that increased abundance of CB1R in liver and epididymal fat alters tissue functionality likely associated with development of systemic metabolic alterations such as insulin resistance in adult mice. All these pathophysiological facts are long-term consequences of nociceptive stress during lactation.
Collapse
|
|
11
|
Yang J, Qiu J, Wang K, Zhu L, Fan J, Zheng D, Meng X, Yang J, Peng L, Fu Y, Zhang D, Peng S, Huang H, Zhang Y. Using molecular functional networks to manifest connections between obesity and obesity-related diseases. Oncotarget 2017; 8:85136-85149. [PMID: 29156709 PMCID: PMC5689599 DOI: 10.18632/oncotarget.19490] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 06/05/2017] [Indexed: 01/04/2023] Open
Abstract
Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease.
Collapse
Affiliation(s)
- Jialiang Yang
- College of Information Engineering, Changsha Medical University, Changsha 410219, P. R. China
| | - Jing Qiu
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| | - Kejing Wang
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| | - Lijuan Zhu
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| | - Jingjing Fan
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| | - Deyin Zheng
- Department of Mathematics, Hangzhou Normal University, Hangzhou 311121, P. R. China
| | - Xiaodi Meng
- Department of Food Science, Fujian Agriculture and Forestry University, Fuzhou 35002, P. R. China
| | - Jiasheng Yang
- Department of Civil and Environmental Engineering, National University of Singapore, Singapore 117576, Singapore
| | - Lihong Peng
- College of Information Engineering, Changsha Medical University, Changsha 410219, P. R. China
| | - Yu Fu
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| | - Dahan Zhang
- Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, P. R. China
| | - Shouneng Peng
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Haiyun Huang
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| | - Yi Zhang
- Department of Mathematics/Network Engineering/Bioscience and Bioengineering/Library, Hebei University of Science and Technology, Shijiazhuang 050018, P. R. China
| |
Collapse
|
|
12
|
Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:9410954. [PMID: 28168013 PMCID: PMC5266865 DOI: 10.1155/2017/9410954] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 12/25/2016] [Indexed: 12/15/2022]
Abstract
Obesity-induced inflammatory changes in white adipose tissue (WAT), which caused dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein-1, contribute to the development of insulin resistance. Moreover, current literature reports state that WAT generates reactive oxygen species (ROS), and the enhanced production of ROS in obese WAT has been closely associated with the dysregulated expression of adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress that results from obesity is thought to be one of the important strategies in preventing and improving lifestyle-related diseases. Exercise training (TR) not only brings about a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the adipokines in WAT. Furthermore, some reports indicate that TR affects the generation of oxidative stress in WAT. This review outlines the impact of TR on the expression of inflammation-related adipokines and oxidative stress in WAT.
Collapse
|
|
13
|
O'brien CM, Poprzeczny A, Dodd JM. Implications of maternal obesity on fetal growth and the role of ultrasound. Expert Rev Endocrinol Metab 2017; 12:45-58. [PMID: 30058877 DOI: 10.1080/17446651.2017.1271707] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Over fifty percent of women entering pregnancy are overweight or obese. This has a significant impact on short and long term maternal and infant health outcomes, and the intergenerational effects of obesity are now a major public health problem globally. Areas covered: There are two major pathways contributing to fetal growth. Glucose and insulin directly affect growth, while other substrates such as leptin, adiponectin and insulin-like growth factors indirectly influence growth through structural and morphological effects on the placenta, uteroplacental blood flow, and regulation of placental transporters. Advances in ultrasonography over the past decade have led to interest in the prediction of the fetus at risk of overgrowth and adiposity utilizing both standard ultrasound biometry and fetal body composition measurements. However, to date there is no consensus regarding the definition of fetal overgrowth, its reporting, and clinical management. Expert commentary: Maternal dietary intervention targeting the antenatal period appear to be too late to sufficiently affect fetal growth. The peri-conceptual period and early pregnancy are being evaluated to determine if the intergenerational effects of maternal obesity can be altered to improve newborn, infant and child health.
Collapse
Affiliation(s)
- Cecelia M O'brien
- a School of Paediatrics and Reproductive Health, and Robinson Research Institute , University of Adelaide , Adelaide , Australia
- b Maternal Fetal Medicine Unit , John Hunter Hospital , Newcastle , Australia
| | - Amanda Poprzeczny
- a School of Paediatrics and Reproductive Health, and Robinson Research Institute , University of Adelaide , Adelaide , Australia
- c Department of Obstetrics and Gynaecology , Lyell McEwin Hospital , Adelaide , Australia
| | - Jodie M Dodd
- a School of Paediatrics and Reproductive Health, and Robinson Research Institute , University of Adelaide , Adelaide , Australia
- d Department of Perinatal Medicine, Women's and Babies Division , Women's and Children's Hospital , Adelaide , Australia
| |
Collapse
|
|
14
|
Boura P, Loukides S, Grapsa D, Achimastos A, Syrigos K. The diverse roles of adiponectin in non-small-cell lung cancer: current data and future perspectives. Future Oncol 2015; 11:2193-203. [DOI: 10.2217/fon.15.96] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In recent years, there is growing research interest for the biological role of adipose tissue-derived bioactive factors, mainly including adipokines, in various forms of cancer. Adiponectin (APN) is the most abundant circulating adipokine, and a key mediator of several cancer-related processes, such as cell proliferation, apoptosis, regulation of tumor cell invasion and angiogenesis. In this review we summarize and critically discuss the published literature on the diverse roles of APN in non-small-cell lung cancer, including its implication in lung cancer development, its use as a diagnostic and prognostic biomarker, and its correlation with cancer-related cachexia. The main challenges and future perspectives, mainly with regard to the potential development of APN-targeted therapeutic agents in cancer therapeutics, are also briefly presented and discussed.
Collapse
Affiliation(s)
- Paraskevi Boura
- Oncology Unit GPP, ‘Sotiria’ General Hospital, Athens School of Medicine, Mesogion 152, 11527, Athens, Greece
| | - Stylianos Loukides
- Oncology Unit GPP, ‘Sotiria’ General Hospital, Athens School of Medicine, Mesogion 152, 11527, Athens, Greece
| | - Dimitra Grapsa
- Oncology Unit GPP, ‘Sotiria’ General Hospital, Athens School of Medicine, Mesogion 152, 11527, Athens, Greece
| | - Apostolos Achimastos
- Oncology Unit GPP, ‘Sotiria’ General Hospital, Athens School of Medicine, Mesogion 152, 11527, Athens, Greece
| | - Konstantinos Syrigos
- Oncology Unit GPP, ‘Sotiria’ General Hospital, Athens School of Medicine, Mesogion 152, 11527, Athens, Greece
| |
Collapse
|
|
15
|
Murray PG, Higham CE, Clayton PE. 60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years. J Endocrinol 2015; 226:T123-40. [PMID: 26040485 DOI: 10.1530/joe-15-0120] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/03/2015] [Indexed: 12/19/2022]
Abstract
At the time of the publication of Geoffrey Harris's monograph on 'Neural control of the pituitary gland' 60 years ago, the pituitary was recognised to produce a growth factor, and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the GH axis has included identification of the key central components of the GH axis: GH-releasing hormone and somatostatin (SST) in the 1970s and 1980s and ghrelin in the 1990s. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980s and 1990s; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses have been defined. Over the same time, spontaneously occurring and targeted mutations in the GH axis in rodents combined with the recognition of genetic causes of familial hypopituitarism demonstrated the key factors controlling pituitary development. As the understanding of the control of GH secretion advanced, developments of treatments for GH axis disorders have evolved. Administration of pituitary-derived human GH was followed by the introduction of recombinant human GH in the 1980s, and, more recently, by long-acting GH preparations. For GH excess disorders, dopamine agonists were used first followed by SST analogues, and in 2005 the GH receptor blocker pegvisomant was introduced. This review will cover the evolution of these discoveries and build a picture of our current understanding of the hypothalamo-GH axis.
Collapse
Affiliation(s)
- P G Murray
- Centre for Paediatrics and Child HealthInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UKDepartment of Paediatric EndocrinologyRoyal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UKDepartment of EndocrinologyThe Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UKCentre for Endocrinology and DiabetesInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK Centre for Paediatrics and Child HealthInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UKDepartment of Paediatric EndocrinologyRoyal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UKDepartment of EndocrinologyThe Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UKCentre for Endocrinology and DiabetesInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK
| | - C E Higham
- Centre for Paediatrics and Child HealthInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UKDepartment of Paediatric EndocrinologyRoyal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UKDepartment of EndocrinologyThe Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UKCentre for Endocrinology and DiabetesInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK Centre for Paediatrics and Child HealthInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UKDepartment of Paediatric EndocrinologyRoyal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UKDepartment of EndocrinologyThe Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UKCentre for Endocrinology and DiabetesInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK
| | - P E Clayton
- Centre for Paediatrics and Child HealthInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UKDepartment of Paediatric EndocrinologyRoyal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UKDepartment of EndocrinologyThe Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UKCentre for Endocrinology and DiabetesInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK Centre for Paediatrics and Child HealthInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UKDepartment of Paediatric EndocrinologyRoyal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UKDepartment of EndocrinologyThe Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UKCentre for Endocrinology and DiabetesInstitute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK
| |
Collapse
|
|
16
|
Fam BC, Sgambellone R, Ruan Z, Proietto J, Andrikopoulos S. Contribution of the hypothalamus and gut to weight gain susceptibility and resistance in mice. J Endocrinol 2015; 225:191-204. [PMID: 25934705 DOI: 10.1530/joe-15-0131] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/30/2015] [Indexed: 12/15/2022]
Abstract
Obesity susceptibility in humans and in rodent strains varies in response to the consumption of high-energy density (HED) diets. However, the exact mechanism(s) involved in this susceptibility remain(s) unresolved. The aim of the present study was to gain greater insight into this susceptibility by using C57BL/6J (B6) mice that were separated into obesity-prone (diet-induced obese (DIO)) and obesity-resistant (diet-induced resistant (DR)) groups following an HED diet for 6 weeks. Physiological, biochemical and gene expression assessments of energy balance were performed in the DIO and DR mice on an HED diet and chow-fed mice. The increased weight gain of the DIO mice as compared to the DR mice was associated with increased energy intake and higher plasma leptin and adiponectin levels but not with reduced physical activity or resting energy expenditure. Hypothalamic Pomc gene expression was elevated, but there were no changes in Npy or Agrp expression. Adipose tissue leptin and adiponectin gene expression were significantly reduced in the DIO group as compared to the DR group. Interestingly, ileum expression of G protein-coupled receptor (Gpr) 40 (Gpr40) was significantly increased, whereas Gpr120, Gpr119, Gpr41, and glucagon-like peptide 1 (Glp1) were reduced. Contrastingly, the lower weight gain of the DR group was associated with elevated adipose tissue leptin and adiponectin gene expression, but there were no differences in plasma hormone or hypothalamic gene expression levels as compared to chow-fed mice. Therefore, the present data demonstrate that susceptibility and resistance to diet-induced weight gain in B6 mice appears to be predominantly driven by peripheral rather than hypothalamic modifications, and changes in gut-specific receptors are a potentially important contributor to this variation.
Collapse
Affiliation(s)
- Barbara C Fam
- Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia
| | - Rebecca Sgambellone
- Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia
| | - Zheng Ruan
- Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia
| | - Joseph Proietto
- Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia
| | - Sofianos Andrikopoulos
- Department of Medicine (Austin Health) Austin Hospital, The University of Melbourne, Level 7, Lance Townsend Building, Studley Road, Heidelberg, Victoria 3084, Australia
| |
Collapse
|
|
17
|
Ghoshal K, Bhattacharyya M. Adiponectin: Probe of the molecular paradigm associating diabetes and obesity. World J Diabetes 2015; 6:151-166. [PMID: 25685286 PMCID: PMC4317307 DOI: 10.4239/wjd.v6.i1.151] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 10/09/2014] [Accepted: 12/17/2014] [Indexed: 02/05/2023] Open
Abstract
Type 2 diabetes is an emerging health challenge all over the world as a result of urbanization, high prevalence of obesity, sedentary lifestyle and other stress related factors compounded with the genetic prevalence. The health consequences and economic burden of the obesity and related diabetes mellitus epidemic are enormous. Different signaling molecules secreted by adipocytes have been implicated in the development of obesity and associated insulin resistance in type 2 diabetes. Human adiponectin, a 244-amino acid collagen-like protein is solely secreted by adipocytes and acts as a hormone with anti-inflammatory and insulin-sensitizing properties. Adiponectin secretion, in contrast to secretion of other adipokines, is paradoxically decreased in obesity which may be attributable to inhibition of adiponectin gene transcription. There are several mechanisms through which adiponectin may decrease the risk of type 2 diabetes, including suppression of hepatic gluconeogenesis, stimulation of fatty acid oxidation in the liver, stimulation of fatty acid oxidation and glucose uptake in skeletal muscle, and stimulation of insulin secretion. To date, no systematic review has been conducted that evaluate the potential importance of adiponectin metabolism in insulin resistance. In this review attempt has been made to explore the relevance of adiponectin metabolism for the development of diabetes mellitus. This article also identifies this novel target for prospective therapeutic research aiming successful management of diabetes mellitus.
Collapse
|
|
18
|
Katergari SA, Passadakis P, Milousis A, Passadaki T, Asimakopoulos B, Mantatzis M, Prassopoulos P, Tripsianis G, Nikolettos N, Papachristou DN. Subcutaneous and total fat at L4-L5 and subcutaneous, visceral and total fat at L3-L4 are important contributors of fasting and postprandial adiponectin levels. Endocr Res 2015; 40:127-32. [PMID: 25774471 DOI: 10.3109/07435800.2014.920349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES Insulin resistance and central obesity have been implicated in the pathogenesis of hypoadiponectinemia in obesity. The aim of this study is to evaluate circulating post-prandial adiponectin in relation to glucose and insulin metabolism, indexes of insulin resistance and sensitivity and, indexes of body fat accumulation and distribution in obese men. METHODS Twenty-eight non-diabetic men underwent an OGTT followed by an oral fat load and were studied at baseline and for 5 h post-prandially for serum adiponectin, glucose and insulin. Insulin resistance was estimated by Homeostasis model assessment (HOMA) and insulin sensitivity by Matsuda index. Body fat accumulation and distribution were evaluated by anthropometric indexes and multiple slices MRI of the abdomen and hip. RESULTS Adiponectin was negatively correlated to insulin levels. Fasting and area under the curve (AUC) adiponectin levels were negatively correlated to HOMA (both p < 0.01) and positively to Matsuda index (both p < 0.05). Negative correlations between fasting adiponectin and total fat (r = -0.408, p < 0.05), AUC adiponectin and subcutaneous, visceral and total fat (r = -0.375, -0.413 and -0.475 respectively, all p < 0.05) at L3-L4 were found, and negative correlations between fasting adiponectin and subcutaneous (r = -0.402, p < 0.05) and total fat (r = -0.491, p < 0.05) and between AUC adiponectin and subcutaneous and total fat (r = -0.506 and -0.547, respectively, both p < 0.01) were present at L4-L5. CONCLUSIONS Circulating adiponectin is inversely correlated to both visceral and subcutaneous fat in non-diabetic men, implying that both compartments are important for adiponectin levels. The best correlation is found at measurement site L4-L5.
Collapse
|
|
19
|
Adya R, Tan BK, Randeva HS. Differential effects of leptin and adiponectin in endothelial angiogenesis. J Diabetes Res 2015; 2015:648239. [PMID: 25650072 PMCID: PMC4310451 DOI: 10.1155/2015/648239] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Accepted: 12/22/2014] [Indexed: 12/11/2022] Open
Abstract
Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD). In relation to this, adipose tissue secreted factors termed "adipokines" have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor) and cardiovascular system (endothelial dysfunction leading to atherosclerosis). Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-κβ and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity.
Collapse
Affiliation(s)
- Raghu Adya
- Division of Translational and Systems Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- *Raghu Adya:
| | - Bee K. Tan
- Division of Translational and Systems Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Department of Obstetrics and Gynaecology, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK
| | - Harpal S. Randeva
- Division of Translational and Systems Medicine-Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| |
Collapse
|
|
20
|
Baldani DP, Skrgatic L, Ougouag R. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women. Int J Endocrinol 2015; 2015:786362. [PMID: 26124830 PMCID: PMC4466395 DOI: 10.1155/2015/786362] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Accepted: 03/26/2015] [Indexed: 01/14/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.
Collapse
Affiliation(s)
- Dinka Pavicic Baldani
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Clinical Hospital Centre, School of Medicine, University of Zagreb, Petrova 13, 10 000 Zagreb, Croatia
| | - Lana Skrgatic
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Clinical Hospital Centre, School of Medicine, University of Zagreb, Petrova 13, 10 000 Zagreb, Croatia
- *Lana Skrgatic:
| | - Roya Ougouag
- School of Medicine, Medical Studies in English, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia
| |
Collapse
|
|
21
|
Obesity indices and metabolic markers are related to hs-CRP and adiponectin levels in overweight and obese females. Obes Res Clin Pract 2014; 7:e315-20. [PMID: 24306161 DOI: 10.1016/j.orcp.2012.05.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2011] [Revised: 04/19/2012] [Accepted: 05/05/2012] [Indexed: 12/21/2022]
Abstract
Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects.
Collapse
|
|
22
|
Nokhbehsaim M, Keser S, Nogueira AVB, Cirelli JA, Jepsen S, Jäger A, Eick S, Deschner J. Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions. J Diabetes Res 2014; 2014:796565. [PMID: 25121107 PMCID: PMC4120919 DOI: 10.1155/2014/796565] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 06/24/2014] [Accepted: 06/25/2014] [Indexed: 01/24/2023] Open
Abstract
Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-α expression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing.
Collapse
Affiliation(s)
- Marjan Nokhbehsaim
- Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany
- Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
| | - Sema Keser
- Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
| | - Andressa Vilas Boas Nogueira
- Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
- Department of Diagnosis and Surgery, School of Dentistry, UNESP, 14801-903 Araraquara, SP, Brazil
| | - Joni Augusto Cirelli
- Department of Diagnosis and Surgery, School of Dentistry, UNESP, 14801-903 Araraquara, SP, Brazil
| | - Søren Jepsen
- Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
- Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, 53111 Bonn, Germany
| | - Andreas Jäger
- Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
- Department of Orthodontics, University of Bonn, 53111 Bonn, Germany
| | - Sigrun Eick
- Department of Periodontology, Laboratory of Oral Microbiology, University of Bern, 3010 Bern, Switzerland
| | - James Deschner
- Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany
- Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
| |
Collapse
|
|
23
|
Sequence variants of ADIPOQ and association with type 2 diabetes mellitus in Taiwan Chinese Han population. ScientificWorldJournal 2014; 2014:650393. [PMID: 25121131 PMCID: PMC4121223 DOI: 10.1155/2014/650393] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Revised: 06/04/2014] [Accepted: 06/16/2014] [Indexed: 01/18/2023] Open
Abstract
Diabetes is a serious global health problem. Large-scale genome-wide association studies identified loci for type 2 diabetes mellitus (T2DM), including adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on risk of T2DM. We attempted to elucidate association between T2DM and polymorphic variations of both in Taiwan's Chinese Han population, with our retrospective case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from Taiwan. Statistical analysis gauged association of these polymorphisms with risk of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with T2DM risk (P = 0.042), with rs2241766 polymorphism being not associated with T2DM (P = 0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299 polymorphism contributes to risk of T2DM in the Taiwanese population.
Collapse
|
|
24
|
Parra-Cordero M, Sepúlveda-Martínez A, Preisler J, Pastén J, Soto-Chacón E, Valdés E, Rencoret G. Role of the glucose tolerance test as a predictor of preeclampsia. Gynecol Obstet Invest 2014; 78:130-5. [PMID: 24903217 DOI: 10.1159/000358876] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Accepted: 01/20/2014] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To determine whether oral glucose tolerance tests (OGTT) play a role as predictors of preeclampsia (PET) in pregnant women. METHODS A retrospective case-control study was conducted in 2,002 singleton pregnancies that had a uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT were adjusted based on maternal characteristics, and the results were expressed as multiples of the expected normal median and compared between groups. Logistic regression analysis was used to determine whether maternal characteristics, OGTT, and UtA Doppler significantly contribute to the prediction of early- (<34 weeks), intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of the screening was determined by ROC curves. RESULTS Women who developed PET were characterized by an older maternal age, an increased body mass index, and an altered UtA Doppler. The group with intermediate-onset PET was the only one associated with higher 2-hour OGTT levels compared to controls. Combined models were developed via logistic regression analysis using maternal characteristics, UtA Doppler, and OGTT to predict PET. These combined models were able to detect around 74, 42, and 21% of women who later developed early-, intermediate-, or late-onset PET, respectively, with only a 5% false-positive rate. CONCLUSIONS This study shows that the combination of maternal characteristics, second-trimester UtA Doppler, and OGTT is a predictor of the development of PET in healthy pregnant women.
Collapse
Affiliation(s)
- M Parra-Cordero
- Fetal Medicine Unit, Department of Obstetrics and Gynecology, University of Chile Hospital, Santiago, Chile
| | | | | | | | | | | | | |
Collapse
|
|
25
|
Anti-Obesity Effect and Action Mechanism ofAdenophora triphyllaRoot Ethanol Extract in C57BL/6 Obese Mice Fed a High-Fat Diet. Biosci Biotechnol Biochem 2014; 77:544-50. [DOI: 10.1271/bbb.120667] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
|
|
26
|
Macis D, Guerrieri-Gonzaga A, Gandini S. Circulating adiponectin and breast cancer risk: a systematic review and meta-analysis. Int J Epidemiol 2014; 43:1226-36. [PMID: 24737805 DOI: 10.1093/ije/dyu088] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND We conducted a meta-analysis in order to investigate whether circulating adiponectin, an insulin-sensitizing hormone produced by adipocytes, is associated with breast cancer risk. METHODS A systematic literature search was performed in PubMed, Medline, EMBASE, ISI Web of Knowledge and the Cochrane Library. The summary relative risk (SRR) was calculated by pooling the different study-specific estimates using the random effect models. Meta-regression, subgroup and sensitivity analyses were carried out to investigate between-study heterogeneity and to test publication bias. RESULTS Data from 15 observational studies, published between 2003 and April 2013 for a total of 4249 breast cancer cases, were analysed. The SRR for the 'highest' vs 'lowest' adiponectin levels indicated a 34% reduction in breast cancer risk [95% confidence interval (CI): 13%-50%]. Between-study heterogeneity was not substantial (I(2)=53%). Ten studies were included in the dose-response analysis: the SRR for an increase of 3 µg/ml of adiponectin corresponded to a 5% risk reduction (95% CI: 1%-9%). The comparison between 'highest' and 'lowest' levels of adiponectin showed an inverse association in postmenopausal women (SRR=0.80; 95% CI: 0.63-1.01) and an indication of an inverse relationship in premenopausal women (SRR=0.72, 95% CI: 0.30-1.72). No evidence of publication bias was found. CONCLUSIONS Low circulating adiponectin levels are associated with an increased breast cancer risk. However, properly designed studies are needed to confirm the role of adiponectin as breast cancer biomarker, and clinical trials should be performed to identify those interventions that may be effective in modulating adiponectin levels and reducing breast cancer risk.
Collapse
Affiliation(s)
- Debora Macis
- Division of Cancer Prevention and Genetics and Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
| | - Aliana Guerrieri-Gonzaga
- Division of Cancer Prevention and Genetics and Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
| | - Sara Gandini
- Division of Cancer Prevention and Genetics and Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
| |
Collapse
|
|
27
|
Knights AJ, Funnell APW, Pearson RCM, Crossley M, Bell-Anderson KS. Adipokines and insulin action: A sensitive issue. Adipocyte 2014; 3:88-96. [PMID: 24719781 PMCID: PMC3979885 DOI: 10.4161/adip.27552] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 12/11/2013] [Accepted: 12/16/2013] [Indexed: 02/06/2023] Open
Abstract
Obesity is a major public health concern and a strong risk factor for insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The last two decades have seen a reconsideration of the role of white adipose tissue (WAT) in whole body metabolism and insulin action. Adipose tissue-derived cytokines and hormones, or adipokines, are likely mediators of metabolic function and dysfunction. While several adipokines have been associated with obese and insulin-resistant phenotypes, a select group has been linked with insulin sensitivity, namely leptin, adiponectin, and more recently, adipolin. What is known about these insulin-sensitizing molecules and their effects in healthy and insulin resistant states is the subject of this review. There remains a significant amount of research to do to fully elucidate the mechanisms of action of these adipokines for development of therapeutics in metabolic disease.
Collapse
Affiliation(s)
- Alexander J Knights
- School of Biotechnology and Biomolecular Sciences; University of New South Wales; Sydney, NSW Australia
| | - Alister PW Funnell
- School of Biotechnology and Biomolecular Sciences; University of New South Wales; Sydney, NSW Australia
| | - Richard CM Pearson
- School of Biotechnology and Biomolecular Sciences; University of New South Wales; Sydney, NSW Australia
| | - Merlin Crossley
- School of Biotechnology and Biomolecular Sciences; University of New South Wales; Sydney, NSW Australia
| | | |
Collapse
|
|
28
|
Hu C, Zhang G, Sun D, Han H, Hu S. Duodenal-jejunal bypass improves glucose metabolism and adipokine expression independently of weight loss in a diabetic rat model. Obes Surg 2014; 23:1436-44. [PMID: 23636998 DOI: 10.1007/s11695-013-0976-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND There is accumulating evidence that adipokines lead to a proinflammatory state, which plays crucial roles in insulin resistance and development of type 2 diabetes mellitus (T2DM). Previous studies demonstrated that weight loss after bariatric surgery is accompanied by a suppression of the proinflammatory state. However, the effect of bariatric surgery on adipokine expression beyond weight loss is still elusive. The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) on glucose homeostasis and adipokine expression independently of weight loss. METHODS A T2DM rat model was developed by a high-fat diet and low dose of streptozotocin. Twenty-one diabetic rats and 10 age-matched SD rats were randomly assigned to the DJB group, sham-DJB (S-DJB) group, and control group. For 12 weeks after surgery, their body weight, food intake, glucose homeostasis, lipid parameters, serum adipokine levels, and adipokine gene expression in the mesocolon adipose tissue were measured. RESULTS Compared to the S-DJB group, DJB induced significant and sustained glycemic control with improved insulin sensitivity and glucose tolerance independently of weight loss. DJB improved the lipid metabolism by decreasing fasting free fatty acids and triglycerides. Serum leptin and IL-6 significantly decreased 12 weeks after DJB, whereas adiponectin increased and TNF-α remained unchanged. The mRNA expression levels of leptin, TNF-α, and IL-6 decreased, whereas adiponectin increased in the mesocolon adipose tissue. CONCLUSION DJB reduced the proinflammatory adipokines and increased the anti-inflammatory adipokines independently of weight loss, which may contribute to the improvement of insulin sensitivity.
Collapse
Affiliation(s)
- Chunxiao Hu
- Department of General Surgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan 250012, Shandong, PR China
| | | | | | | | | |
Collapse
|
|
29
|
Abella V, Scotece M, Conde J, López V, Lazzaro V, Pino J, Gómez-Reino JJ, Gualillo O. Adipokines, metabolic syndrome and rheumatic diseases. J Immunol Res 2014; 2014:343746. [PMID: 24741591 PMCID: PMC3987880 DOI: 10.1155/2014/343746] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 01/10/2014] [Accepted: 01/10/2014] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.
Collapse
Affiliation(s)
- Vanessa Abella
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain ; Department of Molecular and Cellular Biology, University of Coruña (UDC), 15071 A Coruña, Spain
| | - Morena Scotece
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Javier Conde
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Verónica López
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Verónica Lazzaro
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain ; University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
| | - Jesús Pino
- SERGAS, Division of Orthopaedics Surgery and Traumatology, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Juan J Gómez-Reino
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| | - Oreste Gualillo
- SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain
| |
Collapse
|
|
30
|
Kim E, Kim EJ, Seo SW, Hur CG, McGregor RA, Choi MS. Meta-Review of Protein Network Regulating Obesity Between Validated Obesity Candidate Genes in the White Adipose Tissue of High-Fat Diet-Induced Obese C57BL/6J Mice. Crit Rev Food Sci Nutr 2014; 54:910-23. [DOI: 10.1080/10408398.2011.619283] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
|
|
31
|
Serum adiponectin level in diabetic patients with and without Helicobacter pylori infection: is there any difference? ScientificWorldJournal 2014; 2014:402685. [PMID: 24523637 PMCID: PMC3913094 DOI: 10.1155/2014/402685] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 10/24/2013] [Indexed: 12/30/2022] Open
Abstract
Background. Increased insulin resistance is an extragastrointestinal manifestation of Helicobacter pylori (HP) infection. HP changes the level of inflammatory markers and cytokines and changes the adipocyte function by altering the adiponectin level. Given the high prevalence of HP and diabetes in our society, we evaluated the association between HP and serum adiponectin level. In this cross-sectional study, 211 diabetic patients under treatment other than insulin were studied. These patients were divided into two groups of HP+ and HP− based on their HP IgG antibody serology and their blood adiponectin levels were measured. Data was analyzed using independent t-test, Chi-square test, and Fisher's exact test. Results. Seventy-two patients with an average age of 51.56 ± 8.34 years were HP− and 139 patients with an average age of 50.35 ± 9.01 years were HP+. The mean serum adiponectin level in HP− and HP+ groups was 4.54 ± 5.43 and 5.64 ± 3.88 ng/mL, respectively. Insulin resistance degree was significantly higher in HP+ group (HP− = 3.160 ± 3.327 versus HP+ = 4.484 ± 3.781, P = 0.013) but no significant difference was found between the mean serum adiponectin level in HP− and HP+ groups (P = 0.140). Conclusions. Although the insulin resistance degree was significantly higher in HP+ diabetic patients, no significant relationship was found between HP infection and serum levels of adiponectin.
Collapse
|
|
32
|
Fu Y. Adiponectin Signaling and Metabolic Syndrome. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2014; 121:293-319. [DOI: 10.1016/b978-0-12-800101-1.00009-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
33
|
Hsu YJ, Wang LC, Yang WS, Yang CM, Yang CH. Effects of fenofibrate on adiponectin expression in retinas of streptozotocin-induced diabetic rats. J Diabetes Res 2014; 2014:540326. [PMID: 25525608 PMCID: PMC4267464 DOI: 10.1155/2014/540326] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 11/10/2014] [Accepted: 11/10/2014] [Indexed: 12/16/2022] Open
Abstract
Adiponectin has been associated with increased risks of microvascular complications in diabetes; however, its role in the development of diabetic retinopathy (DR) is unknown. Fenofibrate is a lipid-lowering agent that has been shown to be capable of preventing DR progression. We investigated the expression of adiponectin and its receptors in DR and evaluated the effects of fenofibrate on their expression. The mRNA and protein levels of adiponectin and its receptors were elevated in retinas of streptozotocin-induced diabetic rats and were suppressed following fenofibrate treatment. Immunofluorescence staining demonstrated that adiponectin and adipoR1 were expressed in cells located within blood vessels, the retinal ganglion, and the inner nuclear layer. AdipoR1 was strongly expressed whereas adipoR2 was only weekly expressed in vascular endothelial cells. The in vitro experiments showed that adiponectin expression was induced by high glucose concentrations in RGC-5 and RAW264.7 cells and was suppressed following fenofibrate treatment. AdipoR1 and adipoR2 levels in RGC-5 cells were elevated in high glucose concentrations and suppressed by fenofibrate. Our results demonstrated that adiponectin may be a proinflammatory mediator in diabetic retinas and fenofibrate appears to modulate the expression of adiponectin and its receptors in diabetic retinas, effectively reducing DR progression.
Collapse
Affiliation(s)
- Ying-Jung Hsu
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Lu-Chun Wang
- Department of Ophthalmology, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Chung-May Yang
- Department of Ophthalmology, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Chang-Hao Yang
- Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei 100, Taiwan
- *Chang-Hao Yang:
| |
Collapse
|
|
34
|
Napoli N, Strollo R, Paladini A, Briganti SI, Pozzilli P, Epstein S. The alliance of mesenchymal stem cells, bone, and diabetes. Int J Endocrinol 2014; 2014:690783. [PMID: 25140176 PMCID: PMC4124651 DOI: 10.1155/2014/690783] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Accepted: 06/11/2014] [Indexed: 12/15/2022] Open
Abstract
Bone fragility has emerged as a new complication of diabetes. Several mechanisms in diabetes may influence bone homeostasis by impairing the action between osteoblasts, osteoclasts, and osteocytes and/or changing the structural properties of the bone tissue. Some of these mechanisms can potentially alter the fate of mesenchymal stem cells, the initial precursor of the osteoblast. In this review, we describe the main factors that impair bone health in diabetic patients and their clinical impact.
Collapse
Affiliation(s)
- Nicola Napoli
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, MO, USA
- *Nicola Napoli:
| | - Rocky Strollo
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Angela Paladini
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Silvia I. Briganti
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Paolo Pozzilli
- Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
- Centre for Diabetes, The Blizard Building, Barts and The London School of Medicine, Queen Mary, University of London, London, UK
| | - Sol Epstein
- Division of Endocrinology, Mount Sinai School of Medicine, New York, USA
| |
Collapse
|
|
35
|
Song J, Lee JE. Adiponectin as a new paradigm for approaching Alzheimer's disease. Anat Cell Biol 2013; 46:229-34. [PMID: 24386594 PMCID: PMC3875839 DOI: 10.5115/acb.2013.46.4.229] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 11/06/2013] [Accepted: 11/13/2013] [Indexed: 01/03/2023] Open
Abstract
Adiponectin is an adipocytokine released by the adipose tissue and has multiple roles in the immune system and in the metabolic syndromes such as cardiovascular disease, Type 2 diabetes, obesity and also in the neurodegenerative disorders including Alzheimer's disease. Adiponectin regulates the sensitivity of insulin, fatty acid catabolism, glucose homeostasis and anti-inflammatory system through various mechanisms. Previous studies demonstrated that adiponectin modulates memory and cognitive impairment and contributes to the deregulated glucose metabolism and mitochondrial dysfunction observed in Alzheimer's disease. Here, we aim to summarize recent studies that suggest the potential correlation between adiponectin and Alzheimer's disease.
Collapse
Affiliation(s)
- Juhyun Song
- Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Eun Lee
- Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. ; BK21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
36
|
Rigamonti AE, Agosti F, De Col A, Silvestri G, Marazzi N, Bini S, Bonomo S, Giunta M, Cella SG, Sartorio A. Severely obese adolescents and adults exhibit a different association of circulating levels of adipokines and leukocyte expression of the related receptors with insulin resistance. Int J Endocrinol 2013; 2013:565967. [PMID: 24454366 PMCID: PMC3880700 DOI: 10.1155/2013/565967] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Revised: 11/12/2013] [Accepted: 11/19/2013] [Indexed: 12/15/2022] Open
Abstract
Obese adults frequently exhibit a low-grade inflammation and insulin resistance, which have been hypothesized to be established early in childhood. Aim of this study was to evaluate the age-dependent relationships between inflammatory state and insulin resistance in obese adolescents and adults. Clinical and metabolic parameters, circulating adipokines (TNF- α , adiponectin, and leptin), ghrelin, their leukocyte receptors (TNFR1, ADIPOR2, OBRL and GHSR1a), and acute phase reactants (CRP and white blood cells) were assessed in lean and obese adolescents compared with the adult counterparts. Only obese adults had higher HOMA-IR, insulin, and triglycerides compared to the lean group. An inflammatory state was present in obese adolescents and adults, as demonstrated by the higher values of CRP and neutrophils. There were no group differences in circulating levels of TNF- α and leukocyte expression of TNFR1. Adiponectin concentrations and leukocyte expression of ADIPOR2 were higher in the lean groups than in the corresponding obese counterparts. For leptin and leukocyte expression of OBRL, the results were opposed. Circulating levels of ghrelin were higher in lean adolescents and adults than the related lean groups, while there was a higher leukocyte expression of GHSR1a in (only) lean adults than obese adults. When the analysis was performed in (lean or obese) adults, TNF- α , neutrophils, leptin, and GHSR1a were predictors of HOMA-IR. None of the considered independent variables accounted for the degree of insulin resistance in the adolescent group. In conclusion, a dissociation between the low-grade inflammation and insulin resistance is supposed to exist in the early phases of obesity.
Collapse
Affiliation(s)
- Antonello E. Rigamonti
- Department of Clinical Sciences and Community Health, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
| | - Fiorenza Agosti
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Via Ariosto 13, 20145 Milan, Italy
| | - Alessandra De Col
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Via Ariosto 13, 20145 Milan, Italy
| | - Giancarlo Silvestri
- Istituto Auxologico Italiano, IRCCS, Division of Metabolic Diseases, Corso Mameli, 199, 28921 Verbania, Italy
| | - Nicoletta Marazzi
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Via Ariosto 13, 20145 Milan, Italy
| | - Silvia Bini
- Department of Clinical Sciences and Community Health, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
| | - Sara Bonomo
- Department of Clinical Sciences and Community Health, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
| | - Marialuisa Giunta
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Via Ariosto 13, 20145 Milan, Italy
| | - Silvano G. Cella
- Department of Clinical Sciences and Community Health, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
| | - Alessandro Sartorio
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, Via Ariosto 13, 20145 Milan, Italy
- Istituto Auxologico Italiano, IRCCS, Division of Metabolic Diseases, Corso Mameli, 199, 28921 Verbania, Italy
| |
Collapse
|
|
37
|
Waist circumference is a better predictor than body mass index of insulin resistance in type 2 diabetes. Obes Res Clin Pract 2013; 6:e263-346. [PMID: 24331592 DOI: 10.1016/j.orcp.2011.11.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2011] [Revised: 11/20/2011] [Accepted: 11/22/2011] [Indexed: 11/23/2022]
Abstract
UNLABELLED Summay: BACKGROUND Insulin resistance is an important pathogenic factor in type 2 diabetes patents. An easy and efficiency measurement predicting insulin resistance; which can be done easily by type 2 patients is desired. OBJECTIVE To examine whether waist circumference is a better predictor of insulin resistance in type 2 diabetes than body mass index (BMI). METHODS From a population of 1356 registered diabetic patients, 144 who met (1) aged between 30 and 75 years, (2) being Chinese, (3) having had type 2 diabetes for more than one year, and (4) having been taking gliclazide and metformin for more than 6 months were enrolled in this study. The main outcome evaluated is the associations of HOMA insulin resistance index (HOMA index); which were assessed using multiple linear regression analysis. RESULTS The coefficients of multiple regression analysis with stepwise model showed that waist circumference (β = 0.35, p < 0.001) but not BMI (β = 0.01, p = 0.94), adiponectin (β = -0.25, p = 0.04) and hemoglobulin A1c% (HbA1c) (β = 0.25, p = 0.01) were the main predictors of HOMA index. CONCLUSIONS These initial findings indicate that waist circumference is a better predictor of insulin resistance in type 2 diabetes than BMI.
Collapse
|
|
38
|
Mauro L, Pellegrino M, De Amicis F, Ricchio E, Giordano F, Rizza P, Catalano S, Bonofiglio D, Sisci D, Panno ML, Andò S. Evidences that estrogen receptor α interferes with adiponectin effects on breast cancer cell growth. Cell Cycle 2013; 13:553-64. [PMID: 24335340 DOI: 10.4161/cc.27455] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, anti-inflammatory, antiatherogenic, and antiproliferative properties. In addition, it appears to play an important role also in the development and progression of several obesity-related malignancies, including breast cancer. Here, we demonstrated that adiponectin induces a dichotomic effect on breast cancer growth. Indeed, it stimulates growth in ERα+ MCF-7 cells while inhibiting proliferation of ERα- MDA-MB-231 cells. Notably, only in MCF-7 cells adiponectin exposure exerts a rapid activation of MAPK phosphorylation, which is markedly reduced when knockdown of the ERα gene occurred. In addition, adiponectin induces rapid IGF-IR phosphorylation in MCF-7 cells, and the use of ERα siRNA prevents this effect. Moreover, MAPK activation induced by adiponectin was reversed by IGF-IR siRNA. Coimmunoprecipitation studies show the existence of a multiprotein complex involving AdipoR1, APPL1, ERα, IGF-IR, and c-Src that is responsible for MAPK signaling activation in ERα+ positive breast cancer cells. It is well known that in addition to the rapid effects through non-genomic mechanisms, ERα also mediates nuclear genomic actions. In this concern, we demonstrated that adiponectin is able to transactivate ERα in MCF-7 cells. We showed the classical features of ERα transactivation: nuclear localization, downregulation of mRNA and protein levels, and upregulation of estrogen-dependent genes. Thus, our study clarifies the molecular mechanism through which adiponectin modulates breast cancer cell growth, providing evidences on the cell-type dependency of adiponectin action in relationship to ERα status.
Collapse
Affiliation(s)
- Loredana Mauro
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy
| | - Michele Pellegrino
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy
| | - Francesca De Amicis
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy
| | - Emilia Ricchio
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy
| | - Francesca Giordano
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy
| | - Pietro Rizza
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy
| | - Stefania Catalano
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy
| | - Daniela Bonofiglio
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy
| | - Diego Sisci
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy
| | - Maria Luisa Panno
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy
| | - Sebastiano Andò
- Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy
| |
Collapse
|
|
39
|
Nohara K, Liu S, Meyers MS, Waget A, Ferron M, Karsenty G, Burcelin R, Mauvais-Jarvis F. Developmental androgen excess disrupts reproduction and energy homeostasis in adult male mice. J Endocrinol 2013; 219:259-68. [PMID: 24084835 PMCID: PMC3901078 DOI: 10.1530/joe-13-0230] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Polycystic ovary syndrome is a common endocrine disorder in females of reproductive age and is believed to have a developmental origin in which gestational androgenization programs reproductive and metabolic abnormalities in offspring. During gestation, both male and female fetuses are exposed to potential androgen excess. In this study, we determined the consequences of developmental androgenization in male mice exposed to neonatal testosterone (NTM). Adult NTM displayed hypogonadotropic hypogonadism with decreased serum testosterone and gonadotropin concentrations. Hypothalamic KiSS1 neurons are believed to be critical to the onset of puberty and are the target of leptin. Adult NTM exhibited lower hypothalamic Kiss1 expression and a failure of leptin to upregulate Kiss1 expression. NTM displayed an early reduction in lean mass, decreased locomotor activity, and decreased energy expenditure. They displayed a delayed increase in subcutaneous white adipose tissue amounts. Thus, excessive neonatal androgenization disrupts reproduction and energy homeostasis and predisposes to hypogonadism and obesity in adult male mice.
Collapse
Affiliation(s)
- Kazunari Nohara
- Division of Endocrinology, Metabolism and Molecular Medicine and Comprehensive Center on Obesity, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Suhuan Liu
- Division of Endocrinology, Metabolism and Molecular Medicine and Comprehensive Center on Obesity, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Matthew S. Meyers
- Division of Endocrinology, Metabolism and Molecular Medicine and Comprehensive Center on Obesity, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Aurélie Waget
- Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
| | - Mathieu Ferron
- Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
| | - Gérard Karsenty
- Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
| | - Rémy Burcelin
- INSERM U1048, Institute of Metabolic and Cardiovascular Diseases of Rangueil, Toulouse 31432, France
| | - Franck Mauvais-Jarvis
- Division of Endocrinology, Metabolism and Molecular Medicine and Comprehensive Center on Obesity, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- Division of Endocrinology, Department of Medicine Tulane, University Health Sciences Center, New York, NY 10032, USA
| |
Collapse
|
|
40
|
Fuller NR, Lau NS, Denyer G, Caterson ID. An intragastric balloon produces large weight losses in the absence of a change in ghrelin or peptide YY. Clin Obes 2013; 3:172-9. [PMID: 25586733 DOI: 10.1111/cob.12030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Revised: 07/03/2013] [Accepted: 07/29/2013] [Indexed: 12/13/2022]
Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: The development of obesity is a multi-factorial process that results in an alteration in the neuroendocrine hormones that help regulate appetite and body weight. Weight loss has been shown to alter this neuroendocrine balance so as to promote weight regain. An intragastric balloon is an effective method to achieve significant weight loss in obese patients and is well suited for those patients who are looking for an alternative to lifestyle modification alone, and those who are not ready or suitable for surgical intervention. Limited research has shown that the weight loss achieved with an intragastric balloon is mediated by altered secretion of the hormones that regulate appetite and weight. WHAT DOES THIS STUDY ADD?: There are currently limited data on the effects of intragastric balloons on appetite and weight-related hormones. In the current study, we have investigated a broad range of gut hormones and adipokines and their response to weight loss induced by differing methods, and the subsequent effect this may have on weight regain. This is an important research area as novel therapies and long-term strategies are needed to counteract the unfavourable changes to the neuroendocrine control of appetite and satiety associated with diet-induced weight loss. This study aims to determine the effect of weight loss achieved with different methods on fasting levels of appetite hormones. Sixty-six obese adults with metabolic syndrome were randomized to intragastric balloon (IGB) for 6 months, with a 12-month behavioural modification programme (IGB group, 'IGBG') or a 12-month behavioural modification programme alone (control group, 'CG'). Anthropometric assessments and blood samples were taken every 3 months and total ghrelin, peptide YY (PYY), adiponectin and leptin were measured. Significant weight-loss differences favouring the IGBG were evident between groups at all time points. Ghrelin increased when the IGB was in situ (+39.3 pmol L(-1) vs. baseline) and returned to baseline after its removal (-34.7 pmol L(-1) ). Adiponectin and PYY levels remained stable in the IGBG, with transient increases noted in the CG. There were no significant between-group differences for ghrelin, PYY or adiponectin. In the IGBG, despite a decrease in leptin at 6 months (-11.7 ng mL(-1) ), levels increased to baseline after IGB removal (-3.7 ng mL(-1) ). In summary, weight loss associated with the IGB did not alter fasting levels of PYY or adiponectin. There was a return of ghrelin and leptin levels to baseline values after IGB removal. No compensatory rise in ghrelin was evident in either group 12 months after initial weight reduction, suggesting that such treatment strategies may lead to better long-term sustainable weight loss.
Collapse
Affiliation(s)
- N R Fuller
- The Boden Institute, The University of Sydney, Sydney, Australia
| | | | | | | |
Collapse
|
|
41
|
Lozano A, Perez-Martinez P, Marin C, Tinahones FJ, Delgado-Lista J, Cruz-Teno C, Gomez-Luna P, Rodriguez-Cantalejo F, Perez-Jimenez F, Lopez-Miranda J. An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults. Nutr Res 2013; 33:1012-8. [DOI: 10.1016/j.nutres.2013.08.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Revised: 08/26/2013] [Accepted: 08/28/2013] [Indexed: 12/20/2022]
|
|
42
|
Lee AY, Yeo SK, Lee JH, Kim HW, Jia Y, Hoang MH, Chung H, Kim YS, Lee SJ. Hypolipidemic effect of Goami-3 rice (Oryza sativa L. cv. Goami-3) on C57BL/6J mice is mediated by the regulation of peroxisome proliferator-activated receptor-α and -γ. J Nutr Biochem 2013; 24:1991-2000. [DOI: 10.1016/j.jnutbio.2013.06.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 05/03/2013] [Accepted: 06/17/2013] [Indexed: 01/07/2023]
|
|
43
|
Bakker LEH, Sleddering MA, Schoones JW, Meinders AE, Jazet IM. Pathogenesis of type 2 diabetes in South Asians. Eur J Endocrinol 2013; 169:R99-R114. [PMID: 23939919 DOI: 10.1530/eje-13-0307] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The risk of developing type 2 diabetes mellitus (T2DM) is exceptionally high among both native and migrant South Asians. T2DM occurs more often and at a younger age and lower BMI, and the risk of coronary artery and cerebrovascular disease, and renal complications is higher for South Asians compared with people of White Caucasian descent. The high prevalence of T2DM and its related complications in South Asians, which comprise one-fifth of the total world's population, poses a major health and socioeconomic burden. The underlying cause of this excess risk, however, is still not completely understood. Therefore, gaining insight into the pathogenesis of T2DM in South Asians is of great importance. The predominant mechanism, in this ethnicity seems to be insulin resistance (IR) rather than an impaired β-cell function. In this systematic review, we describe several possible mechanisms that may underlie or contribute to the increased IR observed in South Asians.
Collapse
Affiliation(s)
- Leontine E H Bakker
- Department of General Internal Medicine and Endocrinology Walaeus Library, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
| | | | | | | | | |
Collapse
|
|
44
|
Zampino R, Marrone A, Restivo L, Guerrera B, Sellitto A, Rinaldi L, Romano C, Adinolfi LE. Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations. World J Hepatol 2013; 5:528-540. [PMID: 24179612 PMCID: PMC3812455 DOI: 10.4254/wjh.v5.i10.528] [Citation(s) in RCA: 165] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Revised: 08/06/2013] [Accepted: 09/13/2013] [Indexed: 02/06/2023] Open
Abstract
The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus (HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways, oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury (fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV-related diseases (lymphoproliferative disease, atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCV-related diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states.
Collapse
|
|
45
|
Kim HS, Jo J, Lim JE, Yun YD, Baek SJ, Lee TY, Huh KB, Jee SH. Adiponectin as predictor for diabetes among pre-diabetic groups. Endocrine 2013; 44:411-8. [PMID: 23386056 DOI: 10.1007/s12020-013-9890-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2012] [Accepted: 01/19/2013] [Indexed: 12/01/2022]
Abstract
Adiponectin is found to associate with diabetes in studies apart from cohort studies. This prospective cohort study is to evaluate the predictive role of adiponectin in diabetes among participants with impaired fasting glucose (IFG). A total of 42,845 participants who visited 7 health examination centers located in Seoul and Kyunggi province, South Korea, during 2004-2008 were first included. Of the 42,845 participants, 5,085 participants had IFG. IFG was categorized as stage 1 (fasting glucose 100-109 mg/dL) or stage 2 (110-125 mg/dL). The incidence rates of diabetes were followed up to December, 2011. Hazard ratios (HRs) and 95 % confidence intervals (CI) were performed by Cox proportional hazard model. Of the 5,085 participants, 652 participants developed diabetes during a mean follow-up of 4.4 years. Low adiponectin was associated with diabetes among men with stage 2 IFG (HR, 1.78; 95 %CI, 1.33-2.38) while it was associated with diabetes among women with stage 1 IFG (HR, 2.64; 95 %CI, 1.38-5.03) and stage 2 IFG (HR, 2.17; 95 %CI, 1.07-4.42). When combined men and women, the association between adiponectin and diabetes was statistically significant in stage 2 IFG with an increase of about 82 % (HR, 1.82; 95 %CI, 1.40-2.39) after adjusting for age, sex, body mass index, waist circumference, and fasting serum glucose. There was an interaction by sex and stage 1 IFG in the association between adiponectin and risk of diabetes (P < 0.001). Adiponectin was independently associated with diabetes among participants with IFG. This association was apparent in stage 2 IFG. Adiponectin may be used as a predictor of diabetes in patients having IFG.
Collapse
Affiliation(s)
- Hyon-Suk Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Kogan AE, Filatov VL, Kolosova OV, Katrukha IA, Mironova EV, Zhuravleva NS, Nagibin OA, Kara AN, Bereznikova AV, Katrukha AG. Oligomeric adiponectin forms and their complexes in the blood of healthy donors and patients with type 2 diabetes mellitus. J Immunoassay Immunochem 2013; 34:180-96. [PMID: 23537302 DOI: 10.1080/15321819.2012.699494] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric forms, namely low-, medium-, and high-molecular-weight forms. Adn may serve as a risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were (1) to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric forms, (2) to design immunoassays suitable for measuring the Adn forms present in human blood, and (3) to investigate the changes in Adn forms that occur in patients with T2DM. Gel filtration, fluoroimmunoassays, and Western blotting were utilized as major techniques in this study. MAbs recognizing various oligomeric forms of Adn were obtained. Complexes between Adn and complement component C1q and between the low molecular weight form of Adn and albumin were described in human blood. A decrease in the total Adn and Adn-albumin complex levels in the blood of patients with T2DM and no difference in the levels of the Adn-C1q complex in comparison with healthy volunteers were demonstrated. An Adn94-Adn63 fluoroimmunoassay was selected as the technique that most accurately measured the mass ratio of Adn oligomers in blood samples, and an Adn214-Adn27 assay that measured the low-molecular-weight form of Adn only.
Collapse
|
|
47
|
Abstract
Many molecules are involved in the regulation of feeding behavior, and they and their receptors are located in the brain hypothalamus and adipocytes. On the basis of evidence suggesting an association between the brain and adipose tissue, we propose the concept of the brain-adipose axis. This model consists of (l) the expression of endogenous molecules and/or their receptors in the hypothalamus and peripheral adipose tissue, (2) the function of these molecules as appetite regulators in the brain, (3) their existence in the general circulation as secreted proteins and (4) the physiological affects of these molecules on fat cell size and number. These molecules can be divided into two anorexigenic and orexigenic classes. In adipose tissue, all orexigenic molecules possess adipogenic activity, and almost all anorexigenic molecules suppress fat cell proliferation. Although the manner, in which they present in the circulating blood connect the brain and peripheral adipocytes, remains to be well-organized, these observations suggest the positive feedback axis affecting molecules in the hypothalamus and adipose tissue. Analysis of the disturbance and dysregulation of this axis might promote the development of new anti-obesity drugs useful in treating the metabolic syndrome.
Collapse
Affiliation(s)
- Hiroyuki Shimizu
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | | |
Collapse
|
|
48
|
Jee SH, Ahn CW, Park JS, Park CG, Kim HS, Lee SH, Park S, Lee M, Lee CB, Park HS, Kimm H, Choi SH, Sung J, Oh S, Joung H, Kim SR, Youn HJ, Kim SM, Lee HS, Mok Y, Choi E, Yun YD, Baek SJ, Jo J, Huh KB. Serum adiponectin and type 2 diabetes: a 6-year follow-up cohort study. Diabetes Metab J 2013; 37:252-61. [PMID: 23991403 PMCID: PMC3753490 DOI: 10.4093/dmj.2013.37.4.252] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Accepted: 03/19/2013] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. METHODS A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. RESULTS Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. CONCLUSION A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.
Collapse
Affiliation(s)
- Sun Ha Jee
- Institute for Health Promotion, Department of Epidemiology and Health Promotion, Yonsei University Graduate School of Public Health, Seoul, Korea
| | - Chul Woo Ahn
- Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Suk Park
- Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Gyu Park
- Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Hyon-Suk Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang-Hak Lee
- Cardiology Division, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sungha Park
- Cardiology Division, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Myoungsook Lee
- Department of Food and Nutrition, Sungshin Women's University College of Human Ecology, Seoul, Korea
| | - Chang Beom Lee
- Department of Endocrinology and Metabolism, Hanyang University College of Medicine, Seoul, Korea
| | - Hye Soon Park
- Department of Family Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Heejin Kimm
- Institute for Health Promotion, Department of Epidemiology and Health Promotion, Yonsei University Graduate School of Public Health, Seoul, Korea
| | - Sung Hee Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jidong Sung
- Division of Cardiology, Department of Medicine, and Cardiac and Vascular Center, Center for Health Promotion, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seungjoon Oh
- Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea
| | - Hyojee Joung
- Division of Public Health Nutrition, Seoul National University School of Public Health and Institute of Health and Environment, Seoul, Korea
| | - Sung Rae Kim
- Department of Endocrinology and Metabolism, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ho-Joong Youn
- Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sun Mi Kim
- Department of Family Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hong Soo Lee
- Department of Family Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Yejin Mok
- Institute for Health Promotion, Department of Epidemiology and Health Promotion, Yonsei University Graduate School of Public Health, Seoul, Korea
| | - Eunmi Choi
- Institute for Health Promotion, Department of Epidemiology and Health Promotion, Yonsei University Graduate School of Public Health, Seoul, Korea
| | | | | | - Jaeseong Jo
- Institute for Health Promotion, Department of Epidemiology and Health Promotion, Yonsei University Graduate School of Public Health, Seoul, Korea
| | - Kap Bum Huh
- Huh's Diabetes Center and the 21th Century Diabetes and Vascular Research Institute, Seoul, Korea
| |
Collapse
|
|
49
|
Duggan C, Onstad L, Hardikar S, Blount PL, Reid BJ, Vaughan TL. Association between markers of obesity and progression from Barrett's esophagus to esophageal adenocarcinoma. Clin Gastroenterol Hepatol 2013; 11:934-43. [PMID: 23466711 PMCID: PMC3722274 DOI: 10.1016/j.cgh.2013.02.017] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Accepted: 02/18/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes. METHODS We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors. RESULTS Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43-4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09-5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01-4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14-0.82). Metabolic syndrome was not associated with risk of EA. CONCLUSIONS Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE.
Collapse
Affiliation(s)
- Catherine Duggan
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Lynn Onstad
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Sheetal Hardikar
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Patricia L Blount
- Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Medicine, University of Washington, Seattle, WA, USA
| | - Brian J Reid
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Medicine, University of Washington, Seattle, WA, USA,Department of Genome Sciences, University of Washington, Seattle, WA, USA
| | - Thomas L Vaughan
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,Department of Epidemiology, University of Washington, Seattle, WA, USA
| |
Collapse
|
|
50
|
Coradini M, Rand JS, Morton JM, Arai T, Ishioka K, Rawlings JM. Fat mass, and not diet, has a large effect on postprandial leptin but not on adiponectin concentrations in cats. Domest Anim Endocrinol 2013; 45:79-88. [PMID: 23827214 DOI: 10.1016/j.domaniend.2013.06.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Revised: 05/08/2013] [Accepted: 06/04/2013] [Indexed: 10/26/2022]
Abstract
Leptin and adiponectin play important roles in carbohydrate and lipid metabolism in different species. Information is limited on the effects of diet, weight gain, and fat mass on their concentrations in cats. This study compared fasting and postprandial blood leptin and total adiponectin concentrations before and after 8 wk of ad libitum feeding to promote weight gain in adult cats (n = 32) fed either a low-carbohydrate, high-protein (23% and 47% ME) or a high-carbohydrate, low-protein (51% and 21% ME) diet. There were significant effects of total, abdominal, and nonabdominal fat mass, but not diet or body weight, on mean 24-h and peak leptin (P < 0.01); observed increases in mean and peak leptin were greatest for abdominal fat mass (50% and 56% increase for every extra 100 g, respectively). After weight gain, postprandial leptin concentration increased markedly relative to when cats were lean, and the duration of the increase was longer after a mean weight gain of 37% with the low-carbohydrate, high-protein diet group compared with 17% with the high-carbohydrate, low-protein group (P ≤ 0.01). Adiponectin was lower than fasting at some time points during the postprandial period in both groups (P ≤ 0.05). For both fasting and mean 24-h adiponectin, there was no significant diet effect (P ≥ 0.19) or changes in weight gain relative to when cats were lean (P ≥ 0.29). In conclusion, fat mass, and not diet, has a large effect on postprandial leptin but not adiponectin concentrations in cats.
Collapse
Affiliation(s)
- M Coradini
- Centre for Companion Animal Health, School of Veterinary Science, The University of Queensland, Brisbane, QLD 4072, Australia.
| | | | | | | | | | | |
Collapse
|