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Pezzino S, Luca T, Castorina M, Puleo S, Latteri S, Castorina S. Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines. Life (Basel) 2024; 14:93. [PMID: 38255708 PMCID: PMC10820028 DOI: 10.3390/life14010093] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.
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Affiliation(s)
- Salvatore Pezzino
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Tonia Luca
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | | | - Stefano Puleo
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Saverio Latteri
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | - Sergio Castorina
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
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de Luis Román D, Primo Martín D, Izaola Jáuregui O. Association of resistin (rs3138167) gene polymorphism with metabolic response after a hypocaloric Mediterranean diet. NUTR HOSP 2023. [PMID: 37929859 DOI: 10.20960/nh.04763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND the single nucleotide polymorphism (SNP) (rs3138167) of resistin (RETN) gene is a polymorphism that has been associated with metabolic disorder in obese subjects and its effect on the metabolic response after a dietary intervention has not been evaluated. OBJECTIVE our aim was to analyze the effects of the rs3138167 RETN gene polymorphism on metabolic changes secondary to weight loss with a hypocaloric diet with a Mediterranean pattern. METHOD one thousand and eight Caucasian obese patients were evaluated. Before and after 12 weeks on a hypocaloric diet with Mediterranean pattern, an anthropometric evaluation and a biochemical analysis were performed. The statistical analysis was performed as a dominant model (CC vs CT + TT). RESULTS the values of insulin, HOMA-IR and resistin were higher in T allele carriers than non-T allele carriers in pre- and post-intervention time. In non-T allele carriers, resistin, insulin, HOMA-IR, triglycerides and C-reactive protein levels decreased. The improvement was statistically superior in non-T allele carriers; resistin (-1.2 ± 0.2 ng/dl; p = 0.02), triglycerides (-18.3 ± 4.3 mg/dl; p = 0.02), C-reactive protein (-2.6 ± 0.3 mg/dl; p = 0.02), insulin -4.4 ± 1.9 mUI/l; p = 0.02) and HOMA-IR (-2.1 ± 0.7; p = 0.03). CONCLUSION we report an association of rs3138167 with a worse metabolic response (insulin, HOMA-IR, triglyceride and C-reactive protein) in T allele carriers after weight loss with a hypocaloric diet with Mediterranean pattern.
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Affiliation(s)
- Daniel de Luis Román
- Centro de Investigación de Endocrinología y Nutrición Clínica de Valladolid (IENVA). Facultad de Medicina. Universidad de Valladolid
| | - David Primo Martín
- Centro de Investigación de Endocrinología y Nutrición Clínica de Valladolid (IENVA). Facultad de Medicina. Universidad de Valladolid
| | - Olatz Izaola Jáuregui
- Centro de Investigación de Endocrinología y Nutrición Clínica de Valladolid (IENVA). Facultad de Medicina. Universidad de Valladolid
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de Luis D, Primo D, Izaola O, Gómez Hoyos E, López Gómez JJ. Relationship of circulating resistin levels with muscle mass determined by bioelectrical impedance in females with obesity. ENDOCRINOL DIAB NUTR 2023; 70:468-475. [PMID: 37516610 DOI: 10.1016/j.endien.2023.03.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 03/23/2023] [Indexed: 07/31/2023]
Abstract
INTRODUCTION Serum resistin levels have been associated with obesity, visceral fat, and insulin resistance. Its relationship with muscle mass has been less evaluated. OBJECTIVES to evaluate the relationship between muscle mass determined by electrical bioimpedance and circulating resistin levels in obese women over 60 years of age. METHODS We conducted a cross-sectional study in 313 obese women. Anthropometric data (weight, height, body mass index (BMI) and waist circumference), BIA parameters (total fat mass (TFM), fat-free mass (FFM), fat-free mass index (FFMI)), skeletal muscle mass (SMM) and skeletal muscle mass index (SMI)), blood pressure and laboratory tests were recorded. RESULTS Patients were divided into two different groups according to the mean value of SMI (11.93 kg/m2): low SMI versus high SMI. In the low SMI group, the resistin levels were higher than the resistin levels in the high SMI group (delta value: 2.8 + 0.3 ng/dl:p = 0.01). Serum resistin levels are inversely correlated with FFM, FFMI, SMM, and SMI. This adipokine shows a positive correlation with insulin, HOMA-IR and PCR levels. In the model with SMI as the dependent variable, resistin levels explained 12% of the variability in muscle mass (Beta -0.38, 95% CI -0.91 to -0.11). CONCLUSIONS Serum resistin levels are associated with low skeletal muscle mass in obese women over 60 years of age.
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Affiliation(s)
- Daniel de Luis
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Centro de Investigación de Endocrinología y Nutrición (CIEN), Universidad de Valladolid, Valladolid, Spain.
| | - David Primo
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Centro de Investigación de Endocrinología y Nutrición (CIEN), Universidad de Valladolid, Valladolid, Spain
| | - Olatz Izaola
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Centro de Investigación de Endocrinología y Nutrición (CIEN), Universidad de Valladolid, Valladolid, Spain
| | - Emilia Gómez Hoyos
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Centro de Investigación de Endocrinología y Nutrición (CIEN), Universidad de Valladolid, Valladolid, Spain
| | - Juan José López Gómez
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Centro de Investigación de Endocrinología y Nutrición (CIEN), Universidad de Valladolid, Valladolid, Spain
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Primo D, Izaola O, de Luis D. Resistin/uric acid index as a marker of metabolic syndrome in females with obesity. Int J Obes (Lond) 2023; 47:393-398. [PMID: 36864118 DOI: 10.1038/s41366-023-01287-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 02/20/2023] [Accepted: 02/22/2023] [Indexed: 03/04/2023]
Abstract
BACKGROUND The resistin/uric index has been considered a prognostic factor for identifying young people with obesity. Obesity and Metabolic Syndrome (MS) are an important health problem in females. AIMS The objective of this work was to evaluate the relationship of resistin/acid uric index with Metabolic Syndrome on Caucasian females with obesity. METHODS We conducted a cross sectional study in 571 females with obesity. Measurements of anthropometric parameters, blood pressure, fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), lipid profile, C reactive protein, uric acid, resistin and prevalence of Metabolic Syndrome were determined. The resistin/uric acid index was calculated. RESULTS In total, 249 subjects had MS (43.6%). We detected higher levels in the following parameters (Delta; p values); waist circumference (3.1 ± 0.5 cm; p = 0.04), systolic blood pressure (5.3 ± 3.6 mmHg; p = 0.01), diastolic blood pressure (2.3 ± 0.4 mmHg; p = 0.02), glucose levels (7.5 ± 0.9 mg/dL; p = 0.01), insulin levels (2.5 ± 0.3 UI/L; p = 0.02), HOMA-IR (0.7 ± 0.2 units; p = 0.03), uric acid levels (0.9 ± 0.2 mg/dl; p = 0.01), resistin levels (4.1 ± 0.4 ng/dl; p = 0.01) and resistin/uric acid index (0.61 ± 0.01 mg/dl; p = 0.02) in subjects of the high resistin/uric acid index group than low index group. Logistic regression analysis reported a high percentage of hyperglycemia (OR = 1.77, 95% CI = 1.10-2.92; p = 0.02), hypertension (OR = 1.91, 95% CI = 1.36-3.01; p = 0.01), central obesity (OR = 1.48, 95% CI = 1.15-1.84; p = 0.03) and metabolic syndrome percentage (OR = 1.71, 95% CI = 1.22-2.69; p = 0.02) in high resistin/uric acid index group. CONCLUSIONS Resistin/uric acid index is related with Metabolic syndrome (MS) risk and criteria of it in a population of Caucasian females with obesity and this index is a correlated with glucose levels, insulin levels and insulin resistance (HOMA-IR).
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Affiliation(s)
- David Primo
- Endocrinology and Nutrition Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.,Investigation Centre on Endocrinology and Nutrition (IEN), University of Valladolid, Valladolid, Spain
| | - Olatz Izaola
- Endocrinology and Nutrition Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.,Investigation Centre on Endocrinology and Nutrition (IEN), University of Valladolid, Valladolid, Spain
| | - Daniel de Luis
- Investigation Centre on Endocrinology and Nutrition (IEN), University of Valladolid, Valladolid, Spain.
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de Luis DA, Primo D, Izaola O, Aller R. Role of resistin (rs7139228) gene polymorphism with metabolic response after a hypocaloric mediterranean diet. ENDOCRINOL DIAB NUTR 2023; 70:88-97. [PMID: 36841628 DOI: 10.1016/j.endien.2022.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 10/16/2022] [Indexed: 02/25/2023]
Abstract
BACKGROUND The SNP (rs7139228) of the RETN gene is a polymorphism that has been associated with metabolic disorder in subjects with obesity, and its effect on metabolic response after dietary intervention has not been evaluated. OBJECTIVE Our objective was to analyse the effects of the polymorphism of the RETN gene rs7139228 on metabolic changes secondary to weight loss with a hypocaloric Mediterranean diet. DESIGN 1000 obese Caucasian patients were evaluated. An anthropometric evaluation and a biochemical analysis were performed before and after 12 weeks of a hypocaloric Mediterranean diet. The statistical analysis was performed as a dominant model (GG vs GA+AA). RESULTS Improvements in anthropometric parameters, leptin levels and systolic blood pressure were similar in both genotype groups. In non- A allele carriers, levels of resistin, insulin, HOMA-IR, triglycerides and C-reactive protein decreased. The improvements were statistically significant in this group; resistin (-1.3+0.1ng/dL: p=0.02), triglycerides (-22.9+4.9mg/dl: p=0.02), CRP (-2.7+0 0.4mg/dl: p=0.02), insulin -6.5+1.8 mIU/L: p=0.02) and HOMA-IR (-2.2+0.8: p=0, 03). In addition, insulin, HOMA-IR and resistin levels were higher in A allele carriers than in non-carriers. Finally, the prevalence of metabolic syndrome and hyperglycaemia were higher in A allele carriers, and these percentages only decreased after intervention in non-A allele carriers. CONCLUSION The A rs7139228 allele is associated with a worse metabolic response (insulin, HOMA-IR, triglycerides and CRP) after weight loss with a hypocaloric Mediterranean diet. A non-significant decrease in the prevalence of metabolic syndrome and hyperglycaemia were detected in A allele carriers.
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Affiliation(s)
- Daniel Antonio de Luis
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain.
| | - David Primo
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain
| | - Olatz Izaola
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain
| | - Rocío Aller
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain
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Papel del polimorfismo del gen de la resistina (rs7139228) en la respuesta metabólica tras una dieta mediterránea hipocalórica. ENDOCRINOL DIAB NUTR 2022. [DOI: 10.1016/j.endinu.2022.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Martinou E, Pericleous M, Stefanova I, Kaur V, Angelidi AM. Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches. Diagnostics (Basel) 2022; 12:407. [PMID: 35204498 PMCID: PMC8871470 DOI: 10.3390/diagnostics12020407] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/31/2022] [Accepted: 02/02/2022] [Indexed: 02/05/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence is increasing globally. NAFLD is a multifaceted disorder, and its spectrum includes steatosis to steatohepatitis, which may evolve to advanced fibrosis and cirrhosis. In addition, the presence of NAFLD is independently associated with a higher cardiometabolic risk and increased mortality rates. Considering that the vast majority of individuals with NAFLD are mainly asymptomatic, early diagnosis of non-alcoholic steatohepatitis (NASH) and accurate staging of fibrosis risk is crucial for better stratification, monitoring and targeted management of patients at risk. To date, liver biopsy remains the gold standard procedure for the diagnosis of NASH and staging of NAFLD. However, due to its invasive nature, research on non-invasive tests is rapidly increasing with significant advances having been achieved during the last decades in the diagnostic field. New promising non-invasive biomarkers and techniques have been developed, evaluated and assessed, including biochemical markers, imaging modalities and the most recent multi-omics approaches. Our article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, also highlighting the importance of accurate and validated diagnostic tools.
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Affiliation(s)
- Eirini Martinou
- Hepatobiliary and Pancreatic Surgery Department, Royal Surrey County Hospital, Guildford GU2 7XX, UK
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK;
| | - Marinos Pericleous
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK;
- Department of Gastroenterology and Hepatology, Royal Surrey County Hospital, Guildford GU2 7XX, UK
| | - Irena Stefanova
- Department of General Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
| | - Vasha Kaur
- Department of Upper Gastrointestinal and Bariatric Surgery, St George’s Hospital, London SW17 0QT, UK;
| | - Angeliki M. Angelidi
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Ebrahimi R, Shanaki M, Mohassel Azadi S, Bahiraee A, Radmard AR, Poustchi H, Emamgholipour S. Low level of adiponectin predicts the development of Nonalcoholic fatty liver disease: is it irrespective to visceral adiposity index, visceral adipose tissue thickness and other obesity indices? Arch Physiol Biochem 2022; 128:24-31. [PMID: 31482741 DOI: 10.1080/13813455.2019.1661496] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We aimed to study the correlation of adiponectin level with insulin resistance (IR), carotid intima-media thickness (cIMT), and various obesity indices especially visceral adipose tissue (VAT) thickness, and visceral adiposity index (VAI), in patients with NAFLD (n = 41), T2D (n = 22), NAFLD + T2D (n = 41), and healthy subjects (n = 20). Results showed the median level of adiponectin in patients with NAFLD (2.97 μg/mL) and ones with NAFLD + T2D (3.21 μg/mL) is significantly lower rather than in controls (4.39 μg/mL). Moreover, VAI is the only predictor for adiponectin concentration in the combination of patient groups and also in all participants independent of IR and other obesity indices. Adiponectin level had also a positive correlation with cIMT and IR in NAFLD patients. Interestingly, lower level of adiponectin was associated with the presence of T2D, NAFLD, and NAFLD + T2D independent of IR and obesity indices. Collectively, it seems that VAI reflecting visceral adipose tissue function is a possible predictor of adiponectin level.
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Affiliation(s)
- Reyhane Ebrahimi
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehrnoosh Shanaki
- Department of Medical Laboratory Technology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samaneh Mohassel Azadi
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Bahiraee
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Amir Reza Radmard
- Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Solaleh Emamgholipour
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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de Luis D, Aller R, Izaola O, Primo D. Role of the rs10401670 variant in the resistin gene on the metabolic response after weight loss secondary to a high-fat hypocaloric diet with a Mediterranean pattern. J Hum Nutr Diet 2021; 35:722-730. [PMID: 34907604 DOI: 10.1111/jhn.12975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 09/11/2021] [Accepted: 11/11/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND The single nucleotide polymorphism (SNP) (rs10401670) of the RETN gene has been associated with metabolic disorder in obese subjects and has scarcely been evaluated after dietary interventions. The present study aimed to analyse the effects of the rs10401670 RETN gene polymorphism on metabolic changes secondary to weight loss and secondary to a high-fat hypocaloric diet with a Mediterranean dietary pattern. METHODS A Caucasian population comprising 284 obese patients without diabetes mellitus was analysed. Before and after 3 months of a high-fat hypocaloric diet with a Mediterranean pattern, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. A statistical analysis was conducted for the combined CT and TT as a group and for wild-type CC as a second group. RESULTS Decreases in weight, body mass index (BMI), fat mass, systolic blood pressure and waist circumference were similar in both genotypes groups. In T allele carriers, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides and C-reactive protein levels were decreased. The decrease in these parameters was statistically significant for triglycerides (-22.3 ± 9.3 mg dl-1 : p = 0.03), C-reactive protein (-2.8 ± 0.5 mg dl-1 : p = 0.03), insulin (-7.4 ± 2.9 mUI L-1 : p = 0.03) and HOMA-IR (-2.4 ± 1.0: p = 0.02). Leptin levels were decreased in both genotypes groups after the hypocaloric diet, as well as the anthropometric parameters BMI, weight, waist circumference and fat mass. Resistin and adiponectin levels remained unchanged in both groups. CONCLUSIONS In the present study, we have detected a significant association between the T allele of this SNP and a better response of insulin resistance, triglycerides and C-reactive protein compared to non T allele carriers after weight loss with a high-fat hypocaloric diet and a Mediterranean diet.
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Affiliation(s)
- Daniel de Luis
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - Rocío Aller
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - Olatz Izaola
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - David Primo
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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Vadarlis A, Chantavaridou S, Kalopitas G, Bakaloudi DR, Karanika E, Tsekitsidi E, Chourdakis M. Τhe anthropometric and biochemical profile of pediatric non-alcoholic fatty liver disease: A systematic review and a meta-analysis. Clin Nutr 2021; 41:105-121. [PMID: 34872045 DOI: 10.1016/j.clnu.2021.11.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 11/03/2021] [Accepted: 11/18/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and one of the leading indications for liver transplantation in adults. However, current screening methods are inadequate and are accompanied by several disadvantages. This meta-analysis aims to identify the anthropometrical and biochemical characteristics most commonly appearing in pediatric NAFLD that could contribute to the diagnosis of the disease in the every-day clinical setting. METHODS A systematic search was conducted in major electronic databases (MEDLINE, Scopus and Embase) up to 15th of August 2021. Primary outcome was the comparison of the anthropometric characteristics, whereas secondary outcomes were the comparisons of biochemical profile, lipid profile, and metabolic parameters in children with NAFLD compared with age-matched healthy controls. Quality assessment was performed with Newcastle-Ottawa Scale (NOS) and results were expressed as mean differences with 95% confidence intervals. RESULTS Sixty-four studies were included. Two different comparisons were designed regarding the body mass status. Statistically significant differences were demonstrated by comparing children with NAFLD vs lean/normal weighted controls in body weight (23.0 kg, 95% CI: 14.0-31.8, P < 0.00001), height (3.07 cm, 95% CI: 0.21-5.94, P = 0.04), ΒΜΙ (10 kg/m2, 95% CI: 8.36-11.7, P < 0.00001) and waist circumference 25.8 cm (95% CI: 20.6-30.9, P < 0.00001) and by comparing children with NAFLD vs overweight/obese controls in weight (6.81 kg, 95% CI: 3.81-9.81), height (3.18 cm, 95% CI: 1.24 to 5.13, P = 0.001), BMI (2.19 kg/m2, 95% CI: 1.76-2.62, P < 0.00001) and WC (7.35 cm, 95% CI: 6.20-8.49, P < 0.00001). CONCLUSIONS Anthropometrical and biochemical characteristics of children and adolescents with NAFLD are statistically significantly different compared to age-matched controls; these characteristics could be used to identify individuals at risk of developing NAFLD and related comorbidities.
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Affiliation(s)
- Andreas Vadarlis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; Department of Gastroenterology and Hepatology, General Hospital of Thessaloniki "G. Papanikolaou", Greece
| | - Sofia Chantavaridou
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; 4(th) Department of Pediatrics, General Hospital of Thessaloniki, "Papageorgiou", Greece
| | - Georgios Kalopitas
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece; Division of Gastroenterology and Hepatology, 1(st) Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Dimitra Rafailia Bakaloudi
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Evangelia Karanika
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Eirini Tsekitsidi
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece.
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FTO and PLAG1 Genes Expression and FTO Methylation Predict Changes in Circulating Levels of Adipokines and Gastrointestinal Peptides in Children. Nutrients 2021; 13:nu13103585. [PMID: 34684585 PMCID: PMC8538237 DOI: 10.3390/nu13103585] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/03/2021] [Accepted: 10/06/2021] [Indexed: 12/19/2022] Open
Abstract
Adipokines and gastrointestinal tract hormones are important metabolic parameters, and both epigenetic factors and differential gene expression patterns may be associated with the alterations in their concentrations in children. The function of the FTO gene (FTO alpha-ketoglutarate dependent dioxygenase) in the regulation of the global metabolic rate is well described, whereas the influence of protooncogene PLAG1 (PLAG1 zinc finger) is still not fully understood. A cross-sectional study on a group of 26 children with various BMI values (15.3–41.7; median 28) was carried out. The aim was to evaluate the dependencies between the level of methylation and expression of aforementioned genes with the concentration of selected gastrointestinal tract hormones and adipokines in children. Expression and methylation were measured in peripheral blood mononuclear DNA by a microarray technique and a restriction enzyme method, respectively. All peptide concentrations were determined using the enzyme immunoassay method. The expression level of both FTO and PLAG1 genes was statistically significantly related to the concentration of adipokines: negatively for apelin and leptin receptor, and positively for leptin. Furthermore, both FTO methylation and expression negatively correlated with the concentration of resistin and visfatin. Cholecystokinin was negatively correlated, whereas fibroblast growth factor 21 positively correlated with methylation and expression of the FTO gene, while FTO and PLAG1 expression was negatively associated with the level of cholecystokinin and glucagon-like peptide-1. The PLAG1 gene expression predicts an increase in leptin and decrease in ghrelin levels. Our results indicate that the FTO gene correlates with the concentration of hormones produced by the adipose tissue and gastrointestinal tract, and PLAG1 gene may be involved in adiposity pathogenesis. However, the exact molecular mechanisms still need to be clarified.
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12
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Sabry MM, Dawood AF, Rashed LA, Sayed SM, Hassan S, Younes SF. Relation between resistin, PPAR-γ, obesity and atherosclerosis in male albino rats. Arch Physiol Biochem 2020; 126:389-398. [PMID: 30612469 DOI: 10.1080/13813455.2018.1550094] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Obesity and atherosclerosis are inflammatory states involving variable metabolic signals. The adipokine resistin is implicated in adipose tissue dysfunction and is modulated by PPARγ. In this study, resistin and PPARγ role is investigated in the development of CVS disease. Forty-eight Adult male albino rats were divided into control, obesity and atherosclerotic groups; each group is divided into two subgroups; with and without PPARγ agonist administration for 8 weeks. To assess pathological changes; lipid profile, inflammatory mediator, serum resistin level and resistin expression in adipose tissue were measured. Aorta is histopathologically evaluated. It was found that resistin expression is significantly correlated with lipid profile and inflammatory status in obesity and atherosclerotic groups, and PPARγ agonist administration significantly improves inflammatory status and dyslipidemic profile across studied groups (p < .05). Aortic wall shows histopathological evidence of atherosclerosis in obesity group which is more evident in atherosclerotic group, and milder changes upon receiving PPARγ agonist.
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Affiliation(s)
- Maha M Sabry
- Physiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amal F Dawood
- Physiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, KSA
| | - Laila A Rashed
- Biochemistry Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Seham M Sayed
- Physiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sherif Hassan
- Department of Medical Education, California University of Sciences and Medicine, School of Medicine (CalMed-SOM), Irvine, USA
- Anatomy Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sheren F Younes
- Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, KSA
- Pathology Department, Faculty of Medicine, Menoufia University, Cairo, Egypt
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13
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BALTIERI L, CHAIM EA, CHAIM FDM, UTRINI MP, GESTIC MA, CAZZO E. CORRELATION BETWEEN NONALCOHOLIC FATTY LIVER DISEASE FEATURES AND LEVELS OF ADIPOKINES AND INFLAMMATORY CYTOKINES AMONG MORBIDLY OBESE INDIVIDUALS. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:247-251. [PMID: 30540086 DOI: 10.1590/s0004-2803.201800000-62] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/28/2018] [Indexed: 01/01/2023]
Abstract
ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the commonest hepatopathy worldwide. OBJECTIVE: To investigate the correlations between NAFLD histopathological features and the levels of adipokines (adiponectin, leptin, and resistin) and circulating inflammatory markers (interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and C-reactive protein [CRP]). METHODS: This is an exploratory cross-sectional study, which enrolled 19 women with obesity who underwent bariatric surgery. Biochemical characteristics evaluated included the levels of adiponectin, leptin, resistin, IL-6, IL-8, TNF-α, and CRP. NAFLD was assessed through histological examination of liver biopsies carried out during the surgical procedures. RESULTS: The mean age of the study group was 37.3±8.2 years old; mean BMI was 36.2±2.5 kg/m2. Among individuals with liver fibrosis, the levels of IL-8 were significantly higher (24.4 ± 9.7 versus 12.7 ± 6.6; P=0.016726). The intensity of fibrosis presented a significant negative correlation with the levels of adiponectin (R= -0.49379; P=0.03166); i.e. the higher the levels of adiponectin, the lower the intensity of fibrosis. The intensity of steatohepatitis presented a significant negative correlation with the levels of adiponectin (R= -0.562321; P=0.01221); this means that the higher the levels of adiponectin, the lower the intensity of steatohepatitis. CONCLUSION: Adiponectin levels were inversely correlated with the severity of fibrosis and steatohepatitis, whereas IL-8 levels were higher in individuals with liver fibrosis among individuals with obesity and NAFLD undergoing bariatric surgery. The use of these markers to assess NAFLD may bring significant information within similar populations.
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Fang YL, Chen H, Wang CL, Liang L. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”. World J Gastroenterol 2018; 24:2974-2983. [PMID: 30038464 PMCID: PMC6054950 DOI: 10.3748/wjg.v24.i27.2974] [Citation(s) in RCA: 254] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 05/26/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver - which generally follows a benign, non-progressive clinical course - to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of “pediatric” NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.
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Affiliation(s)
- Yan-Lan Fang
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Hong Chen
- College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Chun-Lin Wang
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Li Liang
- Department of Pediatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Li CC, Liu C, Fu M, Hu KQ, Aizawa K, Takahashi S, Hiroyuki S, Cheng J, von Lintig J, Wang XD. Tomato Powder Inhibits Hepatic Steatosis and Inflammation Potentially Through Restoring SIRT1 Activity and Adiponectin Function Independent of Carotenoid Cleavage Enzymes in Mice. Mol Nutr Food Res 2018; 62:e1700738. [PMID: 29266812 DOI: 10.1002/mnfr.201700738] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 12/04/2017] [Indexed: 12/16/2022]
Abstract
SCOPE Beta-carotene-15,15'-oxygenase (BCO1) and beta-carotene-9',10'-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigate the effects of tomato powder (TP containing substantial lycopene (2.3 mg/g)) on NAFLD development and gut microbiome in the absence of both BCO1 and BCO2 in mice. METHOD AND RESULTS BCO1-/- /BCO2-/- double knockout mice were fed a high fat diet (HFD) alone (n = 9) or with TP feeding (n = 9) for 24 weeks. TP feeding significantly reduced pathological severity of steatosis and hepatic triglyceride levels in BCO1-/- /BCO2-/- mice (p < 0.04 vs HFD alone). This was associated with increased SIRT1 activity, nicotinamide phosphoribosyltransferase expression and AMP-activated protein kinase phosphorylation, and subsequently decreased lipogenesis, hepatic fatty acid uptake, and increasing fatty acid β-oxidation (p < 0.05). TP feeding significantly decreased mRNA expression of proinflammatory genes (tnf-α, il-1β, and il-6) in both liver and mesenteric adipose tissue, which were associated with increased plasma adiponectin and hepatic adiponectin receptor-2. Multiplexed 16S rRNA gene sequencing was performed using DNA extracted from cecum fecal samples. TP feeding increased microbial richness and decreased relative abundance of the genus Clostridium. CONCLUSION Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance.
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Affiliation(s)
- Cheng-Chung Li
- Nutrition and Cancer Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Chun Liu
- Nutrition and Cancer Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Maobin Fu
- Nature and Wellness Research Department, Research and Development Division, Kagome Co., Ltd., Tochigi, Japan
| | - Kang-Quan Hu
- Nutrition and Cancer Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Koichi Aizawa
- Nutrition and Cancer Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.,Nature and Wellness Research Department, Research and Development Division, Kagome Co., Ltd., Tochigi, Japan
| | - Shingo Takahashi
- Nature and Wellness Research Department, Research and Development Division, Kagome Co., Ltd., Tochigi, Japan
| | - Suganuma Hiroyuki
- Nature and Wellness Research Department, Research and Development Division, Kagome Co., Ltd., Tochigi, Japan
| | - Junrui Cheng
- Nutrition and Cancer Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Johannes von Lintig
- Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Xiang-Dong Wang
- Nutrition and Cancer Biology Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
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Maffetone PB, Laursen PB. The Prevalence of Overfat Adults and Children in the US. Front Public Health 2017; 5:290. [PMID: 29164096 PMCID: PMC5671970 DOI: 10.3389/fpubh.2017.00290] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 10/19/2017] [Indexed: 12/15/2022] Open
Abstract
The overfat condition is defined as excess body fat sufficient to impair health. The problem exists in most overweight and obese individuals and can also occur in those who are normal-weight and non-obese, often due to excess abdominal fat. Despite previous indications that the prevalence overweight and obesity is leveling, these conditions are currently at their highest levels in US history. Our review estimated the number of overfat Americans at 91% for adults and 69% for children. The primary purpose of this review was to build upon previous estimations of overfat prevalence in developed countries by using new data from the Centers for Disease Control and Prevention to estimate the overfat prevalence in American adults (≥20 years) and children (2-19 years), and to expand the definition of overfat as excess body fat associated with at least one additional risk factor of impaired cardiometabolic or physical health. The secondary goals are to highlight the role of dietary sugar as a primary cause of the overfat pandemic and mention new data showing the increased prevalence of exercise that parallels the rising prevalence of overfat to further emphasize the secondary role exercise may play in fat loss. Current public health guidelines to address the overfat pandemic may require more emphasis on reducing the consumption of refined carbohydrates, including added sugars.
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Affiliation(s)
| | - Paul B. Laursen
- Sports Performance Research Institute New Zealand (SPRINZ), AUT University, Auckland, New Zealand
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17
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Perito ER, Ajmera V, Bass NM, Rosenthal P, Lavine JE, Schwimmer JB, Yates KP, Diehl AM, Molleston JP, Murray KF, Scheimann A, Gill R, Glidden D, Aouizerat B. Association Between Cytokines and Liver Histology in Children with Nonalcoholic Fatty Liver Disease. Hepatol Commun 2017; 1:609-622. [PMID: 29130075 PMCID: PMC5679472 DOI: 10.1002/hep4.1068] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Reliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD histology to gain insight into cellular pathways driving NASH and to identify potential non-invasive discriminators of NAFLD severity and pattern. Methods Cytokines were measured from plasma obtained at enrollment in pediatric participants in NASH Clinical Research Network studies with liver biopsy-proven NAFLD. Cytokines were chosen a priori as possible discriminators of NASH and its components. Minimization of Akaike Information Criterion (AIC) was used to determine cytokines retained in multivariable models. Results Of 235 subjects, 31% had "Definite NASH" on liver histology, 43% had "Borderline NASH", and 25% had NAFLD but not NASH. Total plasminogen activator inhibitor 1 (PAI1) and activated PAI1 levels were higher in pediatric participants with Definite NASH and with lobular inflammation. Interleukin-8 (IL-8) was higher in those with stage 3-4 fibrosis and lobular inflammation. sIL-2rα was higher in children with stage 3-4 fibrosis and portal inflammation. In multivariable analysis, PAI1 variables were discriminators of Borderline/Definite NASH, definite NASH, lobular inflammation and ballooning. IL-8 increased with steatosis and fibrosis severity; sIL-2rα increased with fibrosis severity and portal inflammation. IL-7 decreased with portal inflammation and fibrosis severity. Conclusions Plasma cytokines associated with histology varied considerably among NASH features, suggesting promising avenues for investigation. Future, more targeted analysis is needed to identify the role of these markers in NAFLD and to evaluate their potential as non-invasive discriminators of disease severity.
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Affiliation(s)
- Emily R Perito
- University of California, San Francisco, San Francisco, CA
| | - Veeral Ajmera
- University of California, San Francisco, San Francisco, CA
| | - Nathan M Bass
- University of California, San Francisco, San Francisco, CA
| | | | | | | | | | | | | | | | | | - Ryan Gill
- University of California, San Francisco, San Francisco, CA
| | - David Glidden
- University of California, San Francisco, San Francisco, CA
| | - Bradley Aouizerat
- University of California, San Francisco, San Francisco, CA.,New York University, New York, NY
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18
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New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Protein Cell 2017. [PMID: 28643267 PMCID: PMC5818366 DOI: 10.1007/s13238-017-0436-0] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and a significant global health problem with substantial rise in prevalence over the last decades. It is becoming increasingly clear that NALFD is not only predominantly a hepatic manifestation of metabolic syndrome, but also involves extra-hepatic organs and regulatory pathways. Therapeutic options are limited for the treatment of NAFLD. Accordingly, a better understanding of the pathogenesis of NAFLD is critical for gaining new insight into the regulatory network of NAFLD and for identifying new targets for the prevention and treatment of NAFLD. In this review, we emphasize on the current understanding of the inter-organ crosstalk between the liver and peripheral organs that contributing to the pathogenesis of NAFLD.
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Antonio de Luis D, Aller R, Izaola O, Primo D, Bachiller R. The rs10401670 variant in resistin gene improved insulin resistance response and metabolic parameters secondaries to weight loss after a hypocaloric diet. Clin Nutr ESPEN 2017; 14:14-18. [PMID: 28531393 DOI: 10.1016/j.clnesp.2016.04.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 04/20/2016] [Accepted: 04/20/2016] [Indexed: 11/17/2022]
Abstract
BACKGROUND The SNP 3'UTR C/T (rs10401670), it is a polymorphism that has been associated with diabetes mellitus and it has been scarcely studied before. As far as we know, no studies on interaction among diet intervention, rs10401670 variant of RETN and metabolic response has been realized. OBJECTIVE Our aim was to analyze the effects of the rs10401670 RETN gene polymorphism on insulin resistance response and metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adults obese patients without diabetes mellitus. DESIGN A Caucasian population of 135 obese patients without diabetes mellitus was analyzed. Before and after 3 months on a low fat hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined CT and TT as a group (minor allele group) and wild type CC as second group (major allele group) (dominant model). RESULTS Forty nine patients (36.3%) had the genotype CC (major allele group) and 86 (63.7%) patients had the next genotypes; CT (67 patients, 49.6%) or TT (19 patients, 14.1%) (minor allele group). After dietary treatment and in major allele group, weight, BMI, fat mass, systolic blood pressure and waist circumference decreases were similar than minor allele group. In T allele carriers, fasting plasma glucose, insulin, HOMA-IR, total cholesterol and LDL cholesterol levels decreased significantly. In non T allele carriers and after dietary treatment, only LDL cholesterol and total cholesterol decreased. In non T Allele carriers, the decrease in total cholesterol was -15.1 ± 18.3 mg/dl (decrease in T Allele carriers -18.3 ± 15.7 mg/dl: p > 0.05), LDL-cholesterol was -14.3 ± 18.5 mg/dl (decrease in T Allele carriers -17.3 ± 10.1 mg/dl:p > 0.05), fasting glucose plasma -2.2 ± 1.5 mg/dL (decrease in T Allele carriers -4.8 ± 1.2 mg/dL: p = 0.02), insulin -1.1 ± 2.0 mUI/L (decrease in T Allele carriers -6.3 ± 1.9 mUI/L: p = 0.001) and HOMA-IR -0.2 ± 1.0 (decrease in T Allele carriers -1.8 ± 1.4: p = 0.005). Leptin levels decrease in both genotypes after dietary treatment (-21.1 ± 8.5 ng/dL in nonT Allele carriers vs -16.2 ± 10.2 ng/dL in T Allele carriers:p > 0.05). Resistin remained unchanged in both groups. CONCLUSION In our study in non-diabetic obese subjects, we describe an association of rs10401670T allele with a better metabolic response (glucose, insulin and HOMA-IR) secondary to weight loss with a hypocaloric diet.
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Affiliation(s)
- Daniel Antonio de Luis
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain.
| | - Rocío Aller
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
| | - Olatz Izaola
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
| | - David Primo
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
| | - R Bachiller
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
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Mohamed AA, Sabry S, Abdallah AM, Elazeem NAA, Refaey D, Algebaly HAF, Fath GAE, Omar H. Circulating adipokines in children with nonalcoholic fatty liver disease: possible noninvasive diagnostic markers. Ann Gastroenterol 2017; 30:457-463. [PMID: 28655985 PMCID: PMC5480001 DOI: 10.20524/aog.2017.0148] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Accepted: 03/27/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The growing obesity pandemic is the leading cause for increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in children. Histopathological evaluation of the liver remains the gold standard for NAFLD diagnosis, but it is an invasive procedure with a low but real risk of morbidity and mortality. The current study evaluated circulating chemerin and adiponectin as possible noninvasive diagnostic markers for NAFLD in obese non-diabetic children. METHODS A prospective case-control study was conducted, which included 101 obese children with biopsy-proven NAFLD and 57 age- and sex-matched controls. The overall mean age of the children was 10.08±3.12 years. All underwent a full clinical assessment, routine laboratory investigation, and abdominal ultrasound. Homeostatic model assessment-insulin resistance was calculated and circulating chemerin and adiponectin were evaluated using ELISA. RESULTS Elevated serum chemerin and decreased serum adiponectin were significantly associated with an increased likelihood of exhibiting NAFLD. Receiver operator characteristic curve analysis for differentiation of NAFLD patients from those in the control group demonstrated that chemerin, at a cutoff value of 186.7 ng/mL, yielded a sensitivity and specificity of 56.44% and 87.72% respectively (P<0.001), whereas adiponectin, at a cutoff value of 2.4 µg/mL, had a sensitivity and specificity of 74.26% and 3.51% respectively (P<0.001). Furthermore, body mass index, aspartate transaminase, alanine transaminase, triglycerides, and gamma-glutamyl transferase had significant positive correlations with chemerin and significant negative correlations with adiponectin (P≤0.001). CONCLUSION Circulating chemerin and adiponectin could serve as simple noninvasive diagnostic markers for NAFLD in non-diabetic obese children.
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Affiliation(s)
- Amal Ahmed Mohamed
- Department of Biochemistry, National Hepatology and Tropical Medicine Institute, Egypt (Amal Ahmed Mohmmed)
| | - Said Sabry
- Clinical Pathology, Damanhur National Medical Institute, Egypt (Said Sabry)
| | - Asmaa Mahmoud Abdallah
- Department of Clinical Nutrition, Faculty of Applied Medical Science, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia (Asmaa Mahmoud Abdallah)
| | - Naglaa Adly Abd Elazeem
- Medical Biochemistry Department, Faculty of Medicine, Beni Suef University (Naglaa Adly Abd Elazeem)
| | - Doaa Refaey
- Pediatric Department, Faculty of Medicine, Benha University, Egypt (Doaa Refaey)
| | | | - Gamal Abo El Fath
- Pediatric Department, Genetic Unit, Faculty of Medicine, Ain Shams University (Gamal Abo El Fath)
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University (Heba Omar), Egypt
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21
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Bo L, Yi-Can Y, Qing Z, Xiao-Hui W, Ke H, Chao-Chun Z. Elevated tumour necrosis factor-alpha was associated with intima thickening in obese children. Acta Paediatr 2017; 106:627-633. [PMID: 28036103 DOI: 10.1111/apa.13737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 11/06/2016] [Accepted: 12/28/2016] [Indexed: 11/29/2022]
Abstract
AIM This study investigated the relationship between intima-media thickness (IMT) and immune parameters in obese children from five to 16 years of age. METHODS We enrolled 185 obese children with a mean age of 10.65 ± 2.10 years and 211 controls with a mean age of 10.32 ± 1.81 years. Glycometabolism, lipid metabolism, sex hormones, immune indices and carotid IMT were measured. RESULTS Serum interleukin (IL)-6, IL-10, tumour necrosis factor (TNF)-alpha, white blood cells and common and internal carotid artery IMTs in the obese group were higher than those in the control group (p < 0.05, respectively). Bivariate correlation analysis showed that the common carotid arterial IMT was positively correlated with alanine aminotransferase, triglyceride, uric acid, apolipoprotein B, IL-6, IL-10, TNF-alpha, follicle-stimulating hormone and testosterone. Internal carotid artery IMT was positively correlated with alanine aminotransferase and follicle-stimulating hormone. Both common and internal carotid artery IMTs were inversely correlated with apolipoprotein A1 (p < 0.05, respectively). Stepwise multiple regression analysis showed that testosterone, alanine aminotransferase and TNF-alpha were the independent determinants of common carotid arterial IMT. CONCLUSION Tumour necrosis factor-alpha, alanine aminotransferase and testosterone were associated with intima thickening in the early life in obese children and may increase later risks of premature atherogenicity and adult cardio-cerebrovascular diseases.
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Affiliation(s)
- Luo Bo
- Department of Endocrinology; Children's Hospital of Zhejiang University School of Medicine; Hangzhou China
- Department of Paediatrics; Zhuji People's Hospital; Shaoxing China
| | - Yang Yi-Can
- Department of Endocrinology; Children's Hospital of Zhejiang University School of Medicine; Hangzhou China
| | - Zhou Qing
- Department of Endocrinology; Children's Hospital of Zhejiang University School of Medicine; Hangzhou China
| | - Wu Xiao-Hui
- Department of Endocrinology; Children's Hospital of Zhejiang University School of Medicine; Hangzhou China
| | - Huang Ke
- Department of Endocrinology; Children's Hospital of Zhejiang University School of Medicine; Hangzhou China
| | - Zou Chao-Chun
- Department of Endocrinology; Children's Hospital of Zhejiang University School of Medicine; Hangzhou China
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Tokgöz Y, Işık IA, Akbari S, Kume T, Sayın O, Erdal E, Arslan N. Perilipin polymorphisms are risk factors for the development of obesity in adolescents? A case-control study. Lipids Health Dis 2017; 16:52. [PMID: 28274232 PMCID: PMC5343409 DOI: 10.1186/s12944-017-0440-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 02/27/2017] [Indexed: 11/23/2022] Open
Abstract
Background The variations in perilipin gene (PLIN) were previously associated with obesity. We examined the association of polymorphisms at the PLIN locus in adolescents with obesity and their connection with serum adipokines. Methods A total of 308 children (206 obese, 66.8% and 102 healthy control, 33.2%) between the ages of 10-18 years were included into the study. PLIN gene analysis [PLIN 1, PLIN 4, PLIN 6, PLIN 5’UTR-1234 C > G and PLIN 10171 A/T] were studied by Real Time-PCR. Serum leptin, adiponectin, resistin and ghrelin levels were studied by ELISA method in both groups and their link with perilipin polymorphisms were analyzed. Results Serum leptin level was found significantly high in obese adolescents. Other adipokine levels were similar in both groups. The incidence of PLIN 1, PLIN 4, PLIN 5’UTR-1234 C > G and PLIN 10171 A/T minor and major alleles was similar in both groups. PLIN 6 T/T allele was determined significantly high in obese adolescents compared to that of control group. No correlation was detected between perilipin polymorphism and serum levels of adipokines. Conclusion The PLIN 6 polymorphism of the perilipin gene may influence the risk of the obesity during adolescence. Trial registration Retrospectively registered.
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Affiliation(s)
- Yavuz Tokgöz
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Dokuz Eylul University Faculty of Medicine, 35330, Inciraltı-Izmir, Turkey.
| | - Ishak Abdurrahman Işık
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Dokuz Eylul University Faculty of Medicine, 35330, Inciraltı-Izmir, Turkey
| | - Soheil Akbari
- Department of Medical Biology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey
| | - Tuncay Kume
- Department of Biochemistry, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey
| | - Oya Sayın
- Research Laboratory, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey
| | - Esra Erdal
- Department of Medical Biology, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey
| | - Nur Arslan
- Department of Pediatric Metabolism and Nutrition, Dokuz Eylul University, Faculty of Medicine, Izmir, Turkey
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de Luis DA, Izaola O, Primo D, de la Fuente B, Mulero I, Aller R. The rs1862513 Variant in Resistin Gene-Modified Insulin Resistance and Insulin Levels after Weight Loss Secondary to Hypocaloric Diet. ANNALS OF NUTRITION AND METABOLISM 2017; 69:256-262. [PMID: 28064279 DOI: 10.1159/000453676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 11/21/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Polymorphisms of a single nucleotide in RETN have been associated with indexes of insulin resistance. Our aim was to analyze the effects of the rs1862513 RETN gene polymorphism on insulin resistance, insulin levels, and resistin levels changes after 3 months of a low-fat hypocaloric diet. DESIGN A Caucasian population of 133 obese patients was analyzed before and after 3 months on a low-fat hypocaloric diet. RESULTS Fifty-six patients (42.1%) had the genotype GG (wild group) and 77 (57.9%) patients had the other genotypes; GC (59 patients, 44.4%) or CC (18 patients, 13.5%; mutant group). In wild and mutant genotype groups, weight, body mass index, fat mass, waist circumference, and systolic blood pressure decreased. In the wild genotype group, the decrease in total cholesterol was -13.1 ± 25.3 mg/dL (vs. -4.4 ± 13.7 mg/dL in mutant group: p = 0.004 for group deltas), low density lipoprotein (LDL)-cholesterol was -13.0 ± 21.5 mg/dL (-4.3 ± 10.5 mg/dL: p = 0.007), glucose -7.2 ± 3.5 mg/dL (-0.8 ± 0.2 mg/dL: p = 0.01), insulin -5.6 ± 2.5 mUI/L (-2.9 ± 1.2 mUI/L: p = 0.03) and homeostasis model assessment-insulin resistance (HOMA-IR) -2.5 ± 1.1 (-0.6 ± 1.4: p = 0.02). Leptin levels decreased in both genotypes (-10.1 ± 9.5 ng/dL in wild type group vs. -13.1 ± 0.2 ng/dL in mutant type group: p > 0.05). CONCLUSION The present study suggests that the G/G genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a hypocaloric diet in obese subjects.
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Affiliation(s)
- Daniel Antonio de Luis
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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Antonio de Luis D, Izaola O, Primo D, Aller R, Pacheco D. Effect of two polymorphisms of the resistin gene (rs10401670 and rs1862513) on resistin levels and biochemical parameters in morbidly obese patients 1 year after a biliopancreatic diversion surgery. Clin Nutr 2016; 35:1517-1521. [PMID: 27118275 DOI: 10.1016/j.clnu.2016.04.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Revised: 03/26/2016] [Accepted: 04/02/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND & AIMS Two single nucleotide polymorphisms (SNPs) of the resistin gene RETN have been described: rs10401670 and rs1862513. The objective of this study was to investigate the effect of these SNPs on changes in serum resistin levels, biochemical parameters and weight after biliopancreatic diversion surgery in morbidly obese patients without diabetes mellitus. METHODS A sample of 155 patients with morbid obesity without diabetes mellitus was enrolled. Anthropometric and biochemical evaluations were realized at the basal visit and at 12 months. The percentage of subjects with hypertension and hyperlipidemia was also reported. RESULTS Initial percentage excess weight loss, body mass index, weight, waist circumference, fat mass, blood pressure, low-density lipoprotein cholesterol, total cholesterol, triglycerides levels, insulin and the homeostasis model assessment for insulin sensitivity (HOMA-IR) improve after 12 months. No differences in these improvements were detected between the two genotypes (wild vs mutant group) in each SNP analysis. Resistin levels only changed after surgery in wild genotypes of both SNPs (rs1862513 and rs10401670). The improvement in insulin levels was lower in the mutant group of rs1862513 (-3.4 ± 0.4 UI/dl vs -2.3 ± 0.2 UI/dl; P < 0.05) and rs1040167 (-3.3 ± 0.2 UI/dl vs -1.9 ± 0.3 UI/dl; P < 0.05). The decrease of HOMA-IR was lower in mutant group of rs1862513 (-1.4 ± 0.1 units vs -0.9 ± 0.3 units; P < 0.05) and rs10401670 (-1.2 ± 0.2 units vs -0.9 ± 0.3 units; P < 0.05). CONCLUSIONS The main result of this study was that the mutant genotype of two SNPs of the RETN gene (rs1862513 and rs10401670) was associated with a lack of change in resistin secondary to biliopancreatic diversion. The improvement in insulin levels and HOMA-IR was also lower in these patients.
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Affiliation(s)
- Daniel Antonio de Luis
- Center of Investigation of Endocrinology and Nutrition, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain.
| | - Olatz Izaola
- Center of Investigation of Endocrinology and Nutrition, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - David Primo
- Center of Investigation of Endocrinology and Nutrition, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - Rocio Aller
- Center of Investigation of Endocrinology and Nutrition, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - David Pacheco
- Center of Investigation of Endocrinology and Nutrition, School of Medicine, Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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Jamali R, Arj A, Razavizade M, Aarabi MH. Prediction of Nonalcoholic Fatty Liver Disease Via a Novel Panel of Serum Adipokines. Medicine (Baltimore) 2016; 95:e2630. [PMID: 26844476 PMCID: PMC4748893 DOI: 10.1097/md.0000000000002630] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 12/07/2015] [Accepted: 01/04/2016] [Indexed: 12/28/2022] Open
Abstract
Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers' panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis.This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using "nonalcoholic fatty liver activity score." Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH.Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(-0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (-0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(-0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) - 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (-0.22) yielded a sensitivity and specificity of 90% and 66% respectively, for separating NASH from simple steatosis.New discriminant scores were introduced for differentiating NAFLD/NASH patients with a high accuracy. If verified by future studies, application of suggested models for screening of NAFLD/NASH seems reasonable.
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Affiliation(s)
- Raika Jamali
- From the Research Development Center, Sina Hospital/Digestive Disease Research Institute, Non-Alcoholic Fatty Liver Disease Center, Tehran University of Medical Sciences, Tehran (RJ); Department of Internal Medicine, Shahid Beheshti Hospital (AA, MR); and Research Center for Biochemistry and Nutrition in Metabolic Disease, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran (MHA)
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.
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Asgary S, SamsamShariat SZ, Ghorbani A, Keshvari M, Sahebkar A, Sarrafzadegan N. Relationship between serum resistin concentrations with metabolic syndrome and its components in an Iranian population. Diabetes Metab Syndr 2015; 9:266-270. [PMID: 25311818 DOI: 10.1016/j.dsx.2014.09.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The aim of the study is to determine the association of resistin with each MetS component. METHODS This study had a case-control design, and its data was retrieved from the Isfahan Healthy Heart Program (IHHP), Serum samples from 44 subjects with MetS (diagnosed according to the NCEP-ATPIII criteria) and 46 healthy controls were analyzed for resistin using enzyme-linked immunosorbent assay. Association between serum resistin and levels of total (TC), low- (LDL-C) and high-density (HDL-C) lipoprotein cholesterol, triglycerides (TG), fasting blood sugar (FBS), waist circumference, body mass index, and systolic and diastolic blood pressures was determined. RESULTS Serum resistin levels were significantly higher in the MetS compared with control group (3.64 ± 1.63, P=0.040). Serum levels of resistin were found to be significantly correlated with levels of TC (r=-0.347; P=0.027) and LDL-C (r=-0.311; P=0.050), but not other components of MetS including systolic and diastolic blood pressure, TG, HDL-C and FBS (P>0.05) in the MetS group, after adjustment for age, gender and BMI. No significant correlation between resistin and MetS components was observed in the control group (P>0.05). CONCLUSION Serum resistin levels are elevated in subjects with MetS and may be associated with the severity of this syndrome.
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Affiliation(s)
- Sedigheh Asgary
- Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Seyyed Ziaedin SamsamShariat
- Department of Clinical Biochemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ahmad Ghorbani
- Department of Clinical Biochemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahtab Keshvari
- Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nizal Sarrafzadegan
- Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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Lee SH, Kim D, Baek MY, Tchah H, Kim YS, Ryoo E, Kim YM. Abdominal Subcutaneous Fat Thickness Measured by Ultrasonography Correlates with Hyperlipidemia and Steatohepatitis in Obese Children. Pediatr Gastroenterol Hepatol Nutr 2015; 18:108-14. [PMID: 26157696 PMCID: PMC4493243 DOI: 10.5223/pghn.2015.18.2.108] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 05/12/2015] [Accepted: 05/25/2015] [Indexed: 01/02/2023] Open
Abstract
PURPOSE The aim of this study is to evaluate the relationship between abdominal subcutaneous fat thickness measured by ultrasonography (US) and serum lipid profile and liver transaminases in obese children. METHODS One hundred and sixty-six children diagnosed with obesity from May 2001 to December 2013 were included in this study. Data on serum lipid profile and liver transaminases were collected from clinical records. Abdominal subcutaneous fat thickness and grade of hepatic steatosis were evaluated by US. RESULTS Of the 166 children, 107 were diagnosed with hepatic steatosis by US, 46 with grade I, 56 with grade II, and five children with grade III. According to the grade of hepatic steasosis, the average values of midline abdominal subcutaneous fat thickness and right flank abdominal subcutaneous fat thickness measured 2.9±0.8 cm and 1.9±0.7 cm in the normal group, 3.3±0.8 cm and 2.0±0.7 cm in grade I, 3.8±0.8 cm and 2.3±0.8 cm in grade II, and 4.1±0.8 cm and 2.8±1.4 cm in grade III, respectively. Abdominal subcutaneous fat thickness correlated with grade of hepatic steatosis (p<0.01). In addition, abdominal subcutaneous fat thickness correlated with concentration of serum lipids and liver transaminases in the age group of 12-14 years (p<0.01). CONCLUSION Abdominal subcutaneous fat thickness measured by US can be used as a reliable predictor of possible hyperlipidemia and steatohepatitis in children, especially during the adolescent stage.
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Affiliation(s)
- Sung Hyun Lee
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
| | - Dongwan Kim
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
| | - Min Young Baek
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Hann Tchah
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
| | - Yeon Sun Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Eell Ryoo
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
| | - Yun Mi Kim
- Department of Nursing, Gachon University, Incheon, Korea
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Antiresistin RNA Oligonucleotide Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Attenuating Proinflammatory Cytokines. BIOMED RESEARCH INTERNATIONAL 2015; 2015:414860. [PMID: 25922835 PMCID: PMC4397480 DOI: 10.1155/2015/414860] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 02/19/2015] [Accepted: 03/10/2015] [Indexed: 02/08/2023]
Abstract
The aim of this study was to determine whether inhibition of resistin by a synthetic antiresistin RNA (oligonucleotide) oligo ameliorates metabolic and histological abnormalities in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD) in mice. The antiresistin RNA oligo and a scrambled control oligo (25 mg/kg of body weight) were i.p. injected to HFD mice. Serum metabolic parameters and hepatic enzymes were measured after 4-week treatment. The treatment significantly reduced epididymal fat and attenuated the elevated serum resistin, cholesterol, triglycerides, glucose, and insulin with an improved glucose tolerance test. Antiresistin RNA oligo also normalized serum AST and ALT levels with improved pathohistology of NAFLD. Immunoblotting and qRT-PCR revealed that decreased protein and mRNA expression of resistin in fat and liver tissues of the treated mice were associated with reduction of adipose TNF-α and IL-6 expression and secretion into circulation. mRNA and protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and sterol regulatory element-binding protein-1c (SREBP-1c) were also significantly decreased in the treated mice. Our results suggest that resistin may exacerbate NAFLD in metabolic syndrome through upregulating inflammatory cytokines and hepatic PEPCK and SREBP-1c. Antiresistin RNA oligo ameliorated metabolic abnormalities and histopathology of NAFLD through attenuating proinflammatory cytokines.
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Resistin 420C/G gene polymorphism on circulating resistin, metabolic risk factors and insulin resistance in adult women. Immunol Lett 2014; 162:287-91. [DOI: 10.1016/j.imlet.2014.07.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2014] [Accepted: 07/21/2014] [Indexed: 11/21/2022]
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Boyraz M, Cekmez F, Karaoglu A, Cinaz P, Durak M, Bideci A. Serum adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease. Biomark Med 2014; 7:737-45. [PMID: 24044566 DOI: 10.2217/bmm.13.13] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
AIM To investigate the relationship of adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease (NAFLD). PATIENTS & METHODS Group I consisted of 63 obese children with liver steatosis, group II consisted of 12 obese children with elevated serum ALT activity from group I, and group III included 85 obese children without liver steatosis. RESULTS Leptin levels were higher in the NAFLD children than in the control group. Serum RBP4 levels in obese children with NAFLD were higher than those in obese children without NAFLD and controls. Adiponectin and resistin levels were negatively correlated and RBP4 levels positively correlated with ALT activity and ultrasonographic grading. CONCLUSION These data suggest that adiponectin, resistin and RBP4 may have a role in the pathogenesis of NAFLD in obese children. Adiponectin, leptin, resistin and RBP4 may be suitable markers for predicting metabolic syndrome and NAFLD.
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Affiliation(s)
- Mehmet Boyraz
- Department of Pediatrics, Division of Endocrinology, Şişli Etfal Education & Training Hospital, Istanbul, Turkey
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Abu-Farha M, Behbehani K, Elkum N. Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs. Cardiovasc Diabetol 2014; 13:76. [PMID: 24716628 PMCID: PMC3997236 DOI: 10.1186/1475-2840-13-76] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Accepted: 04/03/2014] [Indexed: 01/05/2023] Open
Abstract
Background Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. Methods We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Results Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47 – 6.19) and (OR = 2.52, 95% CI = 1.45 – 4.35), (OR = 4.26, 95% CI = 2.39 – 7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12 – 0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Conclusion Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs.
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Affiliation(s)
| | | | - Naser Elkum
- Dasman Diabetes Institute, P,O,Box 1180, Dasman 15462, Kuwait.
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Abstract
Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.
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Human resistin inhibits myogenic differentiation and induces insulin resistance in myocytes. BIOMED RESEARCH INTERNATIONAL 2013; 2013:804632. [PMID: 23509781 PMCID: PMC3590612 DOI: 10.1155/2013/804632] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2012] [Revised: 12/06/2012] [Accepted: 12/21/2012] [Indexed: 01/07/2023]
Abstract
This study is aimed to investigate the effect of human resistin on myocyte differentiation and insulin resistance. The human resistin eukaryotic expression vector was stable transfected into C2C12 myocyte cells and was transiently transfected into COS7 cells. The effects of human resistin on cell proliferation, cell cycle, and myogenic differentiation of C2C12 cells were examined. Glucose uptake assays was performed on C2C12 myotubes by using [3H] 2-deoxy-D-glucose. The mRNA levels of insulin receptor (IR) and glucose transporter 4 (GLUT4) were evaluated by semiquantitative RT-PCR. Results showed by the C2C12 cells transfected with human resistin gene compared with that without transfecting gene are as follows: (1) cell proliferation was significantly promoted, (2) after inducing differentiation, the myotube's diameters and expression of desmin and myoglobin decreased, and (3) glucose uptake ratio was lowered and expression of IR and GLUT4 decreased. However, there was no significant difference in the glucose uptake ratio between C2C12 myotubes treated with a human resistin conditioned medium of COS7 cells and treated with control medium. These results suggest that maybe human resistin has not a direct role on insulin sensitivity of myocytes. However, maybe it impaired the insulin sensitivity of myocytes through suppressing myogenesis and stimulating proliferation of myoblasts.
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Kawamoto R, Tabara Y, Kohara K, Kusunoki T, Abe M, Miki T. Plasma Resistin Levels Are Associated with Insulin Resistance in Older Japanese Men from a Rural Village. Metab Syndr Relat Disord 2012; 10:380-6. [DOI: 10.1089/met.2012.0032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Ryuichi Kawamoto
- Department of Community Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yasuharu Tabara
- Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Katsuhiko Kohara
- Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Tomo Kusunoki
- Department of Community Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Masanori Abe
- Department of Community Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Tetsuro Miki
- Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
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Kim JS, Lê KA, Mahurkar S, Davis JN, Goran MI. Influence of elevated liver fat on circulating adipocytokines and insulin resistance in obese Hispanic adolescents. Pediatr Obes 2012; 7:158-64. [PMID: 22434756 PMCID: PMC3767148 DOI: 10.1111/j.2047-6310.2011.00014.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2010] [Revised: 10/21/2011] [Accepted: 10/28/2011] [Indexed: 12/13/2022]
Abstract
OBJECTIVE We performed this study to examine the metabolic differences arising from higher liver fat accumulation in obese Hispanic adolescents, with a particular focus on circulating levels of adipocytokines and insulin resistance. METHODS Forty-one obese Hispanic adolescents (15.3 ± 1.0 years, body mass index percentile: 97.0 ± 3.9) were assessed for: visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat fraction (HFF) by magnetic resonance imaging; fasting measures of serum glucose, insulin and adipocytokines; homeostasis model assessment of insulin resistance (HOMA-IR); and insulin sensitivity (SI) and the acute insulin response to glucose (AIR) by intravenous glucose tolerance test. Subjects with normal levels of HFF (below 5%; n = 25) were compared to those with HFF > 5% (n = 16). RESULTS The two groups differing in HFF were similar for total body fat, VAT and SAT. The group with HFF > 5% had significantly (P < 0.05) higher interleukin-8 (IL-8) (6.1 ± 1.6 vs. 3.2 ± 0.4 pg mL(-1) ), NGF (30.2 ± 9.9 vs. 13.9 ± 1.6 pg mL(-1) ), HOMA-IR (8.8 ± 1.1 vs. 5.5 ± 0.5), AIR (1869 ± 206 vs. 1092 ± 165) and a tendency for lower SI (1.2 ± 0.4 vs. 2.1 ± 0.3; P = 0.06), with no significant differences in any of other factors measured. CONCLUSIONS These data suggest that elevated liver fat is most closely associated with elevated serum IL-8 and NGF levels as well as increased AIR and HOMA-IR. These elevated factors may play significant roles in the metabolic abnormalities associated with elevated liver fat in obese Hispanics.
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Affiliation(s)
- J. S. Kim
- Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - K.-A. Lê
- Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - S. Mahurkar
- Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - J. N. Davis
- Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - M. I. Goran
- Department of Preventive Medicine, Childhood Obesity Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Gupta V, Singh AK, Gupta V, Kumar S, Srivastava N, Jafar T, Pant AB. Association of circulating resistin with metabolic risk factors in Indian females having metabolic syndrome. Toxicol Int 2011; 18:168-72. [PMID: 21976825 PMCID: PMC3183627 DOI: 10.4103/0971-6580.84272] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Role of resistin in insulin sensitivity and metabolic syndrome (MetS) is controversial till date. Increased serum resistin levels are associated with MetS and insulin resistance. The aim of this study was to investigate the relationship between serum resistin levels with markers of the MetS in females. In a cross-sectional study, a total of 170 healthy female subjects were selected for the study. Out of which 71 (age 31.59 ± 4.88 years) were with MetS and 99 (age 31.75 ± 6.34 years) were without MetS. Different parameters of MetS and serum resistin level were measured according to the standard protocols as given in NCEP ATP III 2001 guideline. Serum resistin levels were significantly higher in subjects with MetS when compared with subjects without MetS [13.54 ± 4.14 ng/ml (n = 71) vs. 7.42 ± 2.31 ng/ml (n = 99); P ≤ 0.001]. Resistin levels were positively associated with waist circumference, systolic and diastolic blood pressure, plasma glucose, waist/hip ratio, serum triglycerides, serum cholesterol, serum VLDL, plasma insulin, and insulin resistance, while it was negatively associated with high-density lipoprotein. This study demonstrates a positive correlation between resistin and factors of MetS except high-density lipoprotein which was found to be negatively correlated in Indian female subjects.
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Affiliation(s)
- V Gupta
- Department of Obstetrics and Gynecology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh and RIMS and R Saifai, Etawha Uttar Pradesh, India
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Lack of association of serum resistin levels with metabolic syndrome criteria in obese female patients. Clin Biochem 2011; 44:1280-3. [DOI: 10.1016/j.clinbiochem.2011.09.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Revised: 08/31/2011] [Accepted: 09/04/2011] [Indexed: 01/07/2023]
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Hrabák A, Derzbach L, Csuka I, Bajor T, Körner A. Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity. Inflamm Res 2011; 60:1061-70. [DOI: 10.1007/s00011-011-0367-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2010] [Revised: 06/28/2011] [Accepted: 07/28/2011] [Indexed: 10/17/2022] Open
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Miller MH, Ferguson MAJ, Dillon JF. Systematic review of performance of non-invasive biomarkers in the evaluation of non-alcoholic fatty liver disease. Liver Int 2011; 31:461-73. [PMID: 21382157 DOI: 10.1111/j.1478-3231.2011.02451.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
This systematic review evaluates the many studies carried out to discover and evaluate non-invasive markers of non-alcoholic fatty liver disease (NAFLD). Many different strategies and methods have been used in this task, from the discovery of new markers by global 'shotgun' studies to hypothesis-driven approaches, to the development of algorithm tests based on routinely available clinical and biochemical parameters. We examined the various different approaches, summarising the findings in an attempt to give an overview of the field of non-invasive markers in NAFLD, encompassing markers of steatosis, necro-inflammation and fibrosis. The body of literature surrounding this topic is complex and varied, encompassing not only different methodologies but also different patient characteristics, different disease definitions, as well as different end points. This reflects the heterogeneity of NAFLD, which, however, introduces considerably difficulty when trying to draw a conclusion between studies. We have divided this review into three main chapters based on the characteristics of the studies. The Genomics/Proteomics chapter reviews studies using a non-hypothesis-driven approach to biomarker discovery. Thereafter, we evaluate studies of association - studies that target-specific markers, comparing levels between disease and control groups. Finally, we examine the algorithm tests - mathematical systems developed on the basis of previously described markers and assessed, usually, by receiver operator curve analysis. While radiological examination and investigations offer important diagnostic information, such studies are not discussed in this review - the body of literature surrounding blood and anthropological markers is complex and varied, demanding close attention.
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Affiliation(s)
- Michael H Miller
- Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.
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Sun WL, Chen LL, Zhang SZ, Ren YZ, Qin GM. Changes of adiponectin and inflammatory cytokines after periodontal intervention in type 2 diabetes patients with periodontitis. Arch Oral Biol 2011; 55:970-4. [PMID: 20889139 DOI: 10.1016/j.archoralbio.2010.08.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2010] [Revised: 08/08/2010] [Accepted: 08/09/2010] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To determine serum adiponectin, C-reactive protein (CRP), TNF-α and IL-6 levels in impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) patients with periodontitis before and after periodontal intervention, and to investigate the relationship between T2DM and periodontitis. METHODS A total of 50 IGT and 106 T2DM patients with periodontitis were enrolled. The T2DM patients were divided into two groups: T2DM without macrovascular disease (DM1) group and T2DM with macrovascular disease (DM2) group. Each group was randomly divided into two subgroups according to whether they performed periodontal intervention. The normal control group (NC group) consisted of 30 healthy adults. The serum adiponectin, CRP, TNF-α and IL-6 levels were measured at baseline and 3 months after periodontal intervention. RESULTS The serum adiponectin levels at baseline had decreased tendency with significant difference between each two groups, while CRP, TNF-α, and IL-6 levels had increased tendency with significant difference between each two groups among NC, IGT, DM1 and DM2 groups (all P<0.01). At 3 months after periodontal intervention, the serum adiponectin levels were increased than those without periodontal intervention (all P<0.01), while CRP, IL-6 and TNF-α significantly decreased (all P<0.05) in both IGT and DM1 groups. In DM2 group, only CRP levels at 3 months after periodontal intervention were significantly decreased (P<0.05). Moreover, the HbAlc levels in T2DM patients were improved at 3 months after periodontal invention (P<0.01). CONCLUSION Periodontal intervention is helpful for glucose control, which may be associated with increased serum adiponectin levels and decreased inflammatory cytokine levels.
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Affiliation(s)
- Wei-Lian Sun
- Department of Oral Medicine and Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Street, Hangzhou 310009, PR China
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Silva GH, Hessel G, Coelho KIR, Escanhoela CAF. Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy? SAO PAULO MED J 2011; 129:217-23. [PMID: 21971896 PMCID: PMC10896015 DOI: 10.1590/s1516-31802011000400004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 08/30/2010] [Accepted: 03/28/2011] [Indexed: 01/07/2023] Open
Abstract
CONTEXT AND OBJECTIVE In children, hepatic steatosis may be related to inborn errors of metabolism (IEMs) or to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess and characterize steatosis of indeterminate cause through morphological and morphometric analysis of liver tissue. DESIGN AND SETTING Cross-sectional study at the Departments of Pathology of Faculdade de Ciências Médicas, Universidade Estadual de Campinas (FCM-Unicamp) and Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (FMB-Unesp). METHODS Eighteen consecutive liver biopsies obtained from 16 patients of ages ranging from 3 months to 12 years and nine months that were inserted in a database in the study period were analyzed using optical microscopy and transmission electron microscopy. Through electron microscopy, the mitochondrial density and mean mitochondrial surface area were determined in hepatocytes. Ten patients ranging in age from 1 to 14 years were used as a control group. RESULTS "Pure" steatosis was detected, unaccompanied by fibrosis or any other histological alteration. Microvesicular steatosis predominated, with a significant increase in mean mitochondrial surface area. CONCLUSION Microvesicular steatosis may be related to primary mitochondrial hepatopathy, especially due to reduction of β-oxidation or partial stagnation of oxidative phosphorylation. For these reasons, this form of steatosis (which should not be called "pure") is likely to represent an initial stage in the broad spectrum of NAFLD. We have drawn attention to cases of steatosis in the pediatric group, in which the microvesicular form predominates, since this may be associated with mitochondrial disorders.
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Affiliation(s)
- Gustavo Henrique Silva
- Department of Pediatrics, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
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Padilha PDC, Rocha HFD, Alves N, Peres WAF. Prevalência de doença hepática não-alcoólica em crianças e adolescentes obesos: uma revisão sistemática. REVISTA PAULISTA DE PEDIATRIA 2010. [DOI: 10.1590/s0103-05822010000400016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJETIVO: Revisar publicações que investigaram a prevalência de doença hepática gordurosa não-alcoólica (DHGNA) em crianças. FONTES DE DADOS: Bancos de dados Medline (versão PubMed) e Latin American and Caribbean Centre on Health Sciences Information (LILACS), considerando-se o período de 1997 a 2008. Aplicou-se a combinação dos seguintes descritores: "nonalcoholic fatty liver disease", "hepatic steatosis", "nonalcoholic steatohepatitis", "overweight children", "overweight adolescent", "pediatric obesity", "children obesity", "childhood obesity". SÍNTESE DOS DADOS: Foram selecionados 14 artigos: cinco transversais, um caso-controle e oito de coorte. A concordância entre os avaliadores na classificação da qualidade dos artigos foi considerada ótima (k=0,81), com intervalo de confiança de 95% (0,52-1,00; p<0,001); porém, apenas um estudo foi considerado de excelente qualidade. Todos os estudos demonstraram associação entre obesidade e DHGNA, com prevalências variando de 3,0 a 60,3%. Os artigos analisados indicam que as alterações bioquímicas e de imagem são rapidamente normalizadas com a programação da perda ponderal por meio de dieta e exercício físico. Observam-se prevalências maiores em meninos, com o aumento da idade. Uma associação relatada com frequência foi a da resistência insulínica com a progressão da DHGNA. CONCLUSÕES: São necessários estudos cuidadosamente desenhados para esclarecer a relação entre obesidade e DHGNA na infância. Recomenda-se que todas as crianças obesas sejam rastreadas, já que a DHGNA representa a maior causa de agravo hepático na infância.
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse. This disease includes simple steatosis and nonalcoholic steatohepatitis (NASH). NAFLD/NASH is recognized as a hepatic manifestation of metabolic syndrome. In recent years, pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity. The estimated prevalence of pediatric NAFLD is 2.6%-9.6%, and it is associated with sex, age, and ethnicity. With regard to the pathogenesis of NAFLD, the “two-hit” hypothesis is widely accepted and oxidative stress is thought to play an important role in the second hit. Although clinical symptoms, laboratory data, and imaging findings are important, liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH. In addition, liver biopsy is essential for assessing the degree of necro-inflammatory change and fibrosis in NASH. Two different types of steatohepatitis (type 1 and type 2 NASH) have been reported, with type 2 NASH being present in as many as 51% of pediatric NAFLD patients. However, we and others have observed that type 1 and 2 patterns commonly overlap. Although pharmacotherapy has been studied in clinical trials, lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.
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Ozkol M, Ersoy B, Kasirga E, Taneli F, Bostanci IE, Ozhan B. Metabolic predictors for early identification of fatty liver using doppler and B-mode ultrasonography in overweight and obese adolescents. Eur J Pediatr 2010; 169:1345-52. [PMID: 20499088 DOI: 10.1007/s00431-010-1227-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2010] [Accepted: 05/12/2010] [Indexed: 12/15/2022]
Abstract
(1) to evaluate the frequency of asymptomatic fatty liver disease (FLD) using both Doppler and B-mode ultrasound (US) in overweight and obese adolescents; (2) to compare metabolic findings of fatty liver (FL) assessed by two methods; and (3) to evaluate metabolic predictors of FL shown by these methods. Fifty-nine overweight and obese adolescents aged between 9.0 and 17.0 years and 41 non-obese healthy adolescents were included in this study. B-mode and right hepatic vein Doppler ultrasonography (US) were performed and anthropometric indices, lipid profiles, and adiponectin levels were evaluated in all adolescents. HDL-C levels were significantly lower in patients with FL detected by Doppler US compared to patients without FL (p < 0.05). HDL-C levels were inversely correlated with presence of FL assessed by two methods (r = -0.285, p = 0.004; r = -0.328, p = 0.001, respectively) and adiponectin levels were correlated with presence of FL only detected by B-mode US (r = -0.263, p = 0.008). Adiponectin levels were significantly lower in patients with FL than those without FL assessed by B-Mode US (p = 0.049). Multiple regression analysis revealed that HDL-C levels was the most important predictor of FL assessed by Doppler US (p = 0.027), while body mass index was the determinant of FL assessed by two methods (p < 0.001) in asymptomatic overweight and obese adolescents. It was found that FLD, identified by both B-mode and Doppler US, is seen frequently in asymptomatic overweight and obese adolescents. Elevated BMI is associated with increased risk of FL assessed by two ultrasonographic methods. When using Doppler US, low HDL-C levels can be used as a good predictor for presence of FLD in overweight and obese adolescents.
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Affiliation(s)
- Mine Ozkol
- Department of Radiology, Medical School, Celal Bayar University, Manisa, Turkey
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Circulating visfatin in obese non-diabetic patients in relation to cardiovascular risk factors, insulin resistance, and adipocytokines: A contradictory piece of the puzzle. Nutrition 2010; 26:1130-3. [DOI: 10.1016/j.nut.2008.11.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2008] [Revised: 11/11/2008] [Accepted: 11/13/2008] [Indexed: 11/19/2022]
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de Luis DA, Sagrado MG, Conde R, Aller R, Izaola O, de la Fuente B, Castrillón JLP, Romero E. Relation of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naïve diabetes obese patients. Diabetes Res Clin Pract 2010; 89:110-4. [PMID: 20413173 DOI: 10.1016/j.diabres.2010.03.031] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2010] [Revised: 03/25/2010] [Accepted: 03/30/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND The aim of the present study was to explore the relationship of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naïve diabetic patients. SUBJECTS A population of 66 naïve diabetic patients with obesity was analyzed. A complete nutritional and biochemical evaluation was performed. RESULTS The mean age 56.9+/-11.6 years and the mean BMI was 37.8+/-6.3. Patients were divided in two groups by median resistin value (3.3ng/ml), group I (patients with the low values, average value 2.5+/-0.5) and group II (patients with the high values, average value 4.8+/-1.8). Patients in the group I had lower waist circumference, total cholesterol, LDL-cholesterol and C-reactive protein than patients in group II. Correlation analysis showed a significant correlation among resistin levels and the independent variables; BMI (r=0.26; p<0.05), waist circumference (r=0.38; p<0.05), fat mass (r=0.28; p<0.05), LDL-cholesterol (r=0.3; p<0.05), C-reactive protein (r=0.28; p<0.05). In the multivariate analysis, resistin concentration increase 0.024ng/ml (CI 95%: 0.006-0.42) for each mg/dl of C-reactive protein. CONCLUSION Circulating resistins are associated with C-reactive protein in an independent way in naïve diabetic patients.
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Affiliation(s)
- D A de Luis
- Institute of Endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, RD-056/0013 RETICEF, University of Valladolid, C/Los Perales 16, Simancas 47130, Valladolid, Spain.
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Duarte MASDM, Silva GAPD. Obesity in children and adolescents: the relation between metabolic syndrome and non-alcoholic fatty-liver disease. REVISTA BRASILEIRA DE SAÚDE MATERNO INFANTIL 2010. [DOI: 10.1590/s1519-38292010000200004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
This article aims to review clinical and diagnostic aspects of non-alcoholic fatty liver disease associated with obesity and its relation to metabolic syndrome in children and adolescents. An on-line search was carried out of original articles in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Eletronic Library Online (SciELO) databases, using the following key words: "hepatic steatosis", "nonalcoholic fatty liver diseases", "overweight", "obesity", "children", "adolescents", "ultrasound" and "metabolic syndrome" in English and Portuguese. Two hundred and seventy-five articles were initially selected, all published between 1993 and 2008. After reading this was narrowed down to 67. The literature consulted revealed no consensus regarding the need to screen for metabolic syndrome and non-alcoholic fatty liver disease, especially in obese children and adolescents and those who have excess fat in the abdominal region. An ultrasound examination of the liver is typically used for screening and, in the case of children who present alterations in aminotransferases in addition to fatty infiltration of the liver, a strict clinical follow-up and a liver biopsy are recommended if these symptoms do not disappear on treatment.
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Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease. Adv Med Sci 2010; 54:177-82. [PMID: 20022856 DOI: 10.2478/v10039-009-0047-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
PURPOSE Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in patomechanism of this disease is not clear. The aim of the study was to evaluate the serum levels of leptin, adiponectin and resistin in obese children with NAFLD. MATERIAL/METHODS The fasting serum levels of adipokines were determined in 44 consecutive obese children with suspected liver disease and in 24 lean controls. The degree of the ultrasound liver steatosis was graded according to Saverymuttu. RESULTS The fatty liver was confirmed in 33 children by ultrasonography (16 of them also showed an increased ALT activity). The serum leptin level was significantly higher and adiponectin level was lower in the obese children with NAFLD when compared to controls. Only adiponectin correlated with homeostasis model assessment of insulin resistance (HOMA-IR). Significant negative correlations were found between the ultrasonographic grades of liver steatosis and adiponectin and resistin levels. Serum adiponectin and resistin levels were lower in children with an advanced liver steatosis (grade 3, n=10) compared to patients with a mild steatosis (grade 1-2, n=23). The ability of serum adiponectin and resistin to differentiate children with an advanced liver steatosis from those with mild steatosis was significant. CONCLUSIONS These data suggest a role of both adiponectin and resistin in the pathogenesis of NAFLD in obese children and confirm the association between adiponectin and insulin resistance. Adiponectin and resistin may be suitable serum markers in predicting an advanced liver steatosis in children with NAFLD.
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Nobili V, Alisi A, Raponi M. Pediatric non-alcoholic fatty liver disease: Preventive and therapeutic value of lifestyle intervention. World J Gastroenterol 2009; 15:6017-22. [PMID: 20027672 PMCID: PMC2797656 DOI: 10.3748/wjg.15.6017] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), and eventually cirrhosis and liver failure, is seen to be increasing amongst Western children. NAFLD rates are rising in parallel with the epidemic of childhood obesity, and in particular, fatty liver evolves more easily in NASH when poor dietary habits and sedentary lifestyle are combined. In fact, its general prevalence in the child population varies between 2.6% and 10%, but increases up to 80% in obese children. Since NASH is expected to become the most common cause of pediatric chronic liver disease in the near future, there is broad interest amongst clinical researchers to move forward, both in diagnosis and treatment. Unfortunately, to date, the expensive and invasive procedure of liver biopsy is seen as the gold standard for NASH diagnosis and few noninvasive diagnostic methods can be applied successfully. Moreover, there are still no approved pharmacological interventions for NAFLD/NASH. Therefore, current management paradigms are based upon the presence of associated risk factors and aims to improve an individual’s quality of life, thus reducing NAFLD-associated morbidity and mortality. Today, lifestyle intervention (diet and exercise) is the treatment of choice for NAFLD/NASH. Thus far, no study has evaluated the potential preventive effect of lifestyle intervention on children at risk of NAFLD/NASH. Future studies will be required in this area with the perspective of developing a national program to promote nutrition education and increase physical activity as means of preventing the disease in individuals at risk. Here, we outline the clinical course, pathogenesis and management of NAFLD in children, highlighting the preventive and therapeutic value of lifestyle intervention.
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