scholarly journals Plasma Adiponectin in Nonalcoholic Fatty Liver Is Related to Hepatic Insulin Resistance and Hepatic Fat Content, Not to Liver Disease Severity

2005 ◽  
Vol 90 (6) ◽  
pp. 3498-3504 ◽  
Author(s):  
Elisabetta Bugianesi ◽  
Uberto Pagotto ◽  
Rita Manini ◽  
Ester Vanni ◽  
Amalia Gastaldelli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Female Gender ◽  
Fat Content ◽  
Hepatic Insulin Resistance ◽  
Nonalcoholic Fatty Liver ◽  
Plasma Adiponectin ◽  
Histological Features ◽  
The Metabolic Syndrome ◽  
Hepatic Fat

Plasma levels of adiponectin are decreased in patients with nonalcoholic fatty liver disease (NAFLD), but the relationship among plasma adiponectin, insulin sensitivity, and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentrations in relation to 1) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); 2) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and 3) histological features at liver biopsy (n = 116). When the data from all subjects were combined, plasma adiponectin levels were positively associated with increased age, female gender, and plasma high-density lipoprotein levels, and negatively associated with waist circumference, body mass index, triglycerides, indices of insulin resistance, and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In step-wise regression, increased age, female gender, waist circumference, triglyceride levels, and homeostasis model assessment independently associated with adiponectin (adjusted R2, 0.329). In NAFLD, adiponectin was only associated with increased age, female gender, and triglycerides (adjusted R2, 0.245). When the measured histological parameters were included in the model, plasma adiponectin levels were also inversely proportional to the percentage of hepatic fat content (adjusted R2, 0.221), whereas necroinflammation and fibrosis did not fit in the model. Adiponectin was negatively correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.

scholarly journals Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Oral Glucose ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

scholarly journals Hepatitis C Virus-Infected Patients Are ‘Spared’ from the Metabolic Syndrome but Not from Insulin Resistance. A Comparative Study of Nonalcoholic Fatty Liver Disease and Hepatitis C Virus-Related Steatosis

2009 ◽  
Vol 23 (4) ◽  
pp. 273-278 ◽  
Author(s):  
Amedeo Lonardo ◽  
Stefano Ballestri ◽  
Luigi E Adinolfi ◽  
Enrico Violi ◽  
Lucia Carulli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C feature steatosis and insulin resistance (IR), conditions associated with the metabolic syndrome (MS).OBJECTIVES: To assess the prevalence of MS and determinants of IR in patients with NAFLD and chronic hepatitis C.METHODS: Ninety-three consecutive patients with NAFLD, 97 with chronic hepatitis C virus (HCV) genotypes 1 and 2, and 182 ‘healthy’ controls without steatosis were enrolled in the present study. The prevalence of MS was assessed by modified Adult Treatment Panel III criteria and IR by the homeostasis model assessment of insulin resistance (HOMA-IR). IR was defined as the 75th percentile of the HOMA-IR of control subjects.RESULTS: While the prevalence of IR was similar in NAFLD and HCV-infected subjects (70.0% and 78.7%, respectively), the prevalence of MS was significantly higher in NAFLD patients than in HCV-infected patients (27.9% versus 4.1%) and in controls (5.6%). With multivariate analysis, IR was predicted by body mass index (OR 1.263; 95% CI 1.078 to 1.480) and triglyceridemia (OR 1.011; 95% CI 1.002 to 1.020) in NAFLD and by sex (OR for female sex 0.297; 95% CI 0.094 to 0.940) and fibrosis stage (OR 2.751; 95% CI 1.417 to 5.340) in chronic hepatitis C.CONCLUSIONS: IR is independently associated with body mass index and triglyceridemia in NAFLD, sex and fibrosis in chronic HCV infection, and has a higher prevalence in NAFLD and chronic hepatitis C than in controls. However, the frequency of MS in HCV-infected patients, similar to that of controls, is significantly lower than that seen in NAFLD patients. The current diagnostic criteria of MS are more likely to ‘capture’ patients with NAFLD than with chronic hepatitis C, although both groups are insulin resistant.

Nonalcoholic steatohepatitis

2010 ◽  
pp. 2480-2482
Author(s):  
Stephen F. Stewart ◽  
Chris P. Day
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
Liver Disorder ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Developed World ◽  
Nonalcoholic Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the developed world, affecting 20 to 30% of Western adults. Nonalcoholic liver disease occurs with a range of severity from simple steatosis through nonalcoholic steatohepatitis (NASH) to fatty fibrosis—and, ultimately, cirrhosis. The condition is a manifestation of the metabolic syndrome, strongly associated with obesity, insulin resistance, and dyslipidaemia; dietary and genetic factors appear to determine susceptibility to the disease and its progression....

scholarly journals Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine

2010 ◽  
Vol 299 (5) ◽  
pp. G1068-G1077 ◽  
Author(s):  
Elango Kathirvel ◽  
Kengathevy Morgan ◽  
Ganesh Nandgiri ◽  
Brian C. Sandoval ◽  
Marie A. Caudill ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Signaling Pathways ◽  
Hepg2 Cells ◽  
Fasting Glucose ◽  
Hepatic Insulin Resistance ◽  
Nonalcoholic Fatty Liver ◽  
Downstream Signaling ◽  
Insulin Resistant ◽  
Hepatic Fat

Nonalcoholic fatty liver (NAFL) is a common liver disease, associated with insulin resistance. Betaine has been tested as a treatment for NAFL in animal models and in small clinical trials, with mixed results. The present study aims to determine whether betaine treatment would prevent or treat NAFL in mice and to understand how betaine reverses hepatic insulin resistance. Male mice were fed a moderate high-fat diet (mHF) containing 20% of calories from fat for 7 (mHF) or 8 (mHF8) mo without betaine, with betaine (mHFB), or with betaine for the last 6 wk (mHF8B). Control mice were fed standard chow containing 9% of calories from fat for 7 mo (SF) or 8 mo (SF8). HepG2 cells were made insulin resistant and then studied with or without betaine. mHF mice had higher body weight, fasting glucose, insulin, and triglycerides and greater hepatic fat than SF mice. Betaine reduced fasting glucose, insulin, triglycerides, and hepatic fat. In the mHF8B group, betaine treatment significantly improved insulin resistance and hepatic steatosis. Hepatic betaine content significantly decreased in mHF and increased significantly in mHFB. Betaine treatment reversed the inhibition of hepatic insulin signaling in mHF and in insulin-resistant HepG2 cells, including normalization of insulin receptor substrate 1 (IRS1) phosphorylation and of downstream signaling pathways for gluconeogenesis and glycogen synthesis. Betaine treatment prevents and treats fatty liver in a moderate high-dietary-fat model of NAFL in mice. Betaine also reverses hepatic insulin resistance in part by increasing the activation of IRS1, with resultant improvement in downstream signaling pathways.

scholarly journals Plasma adiponectin is decreased in nonalcoholic fatty liver disease

2005 ◽  
Vol 152 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Claudio Pagano ◽  
Giorgio Soardo ◽  
Walter Esposito ◽  
Francesco Fallo ◽  
Lorenza Basan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Plasma Adiponectin ◽  
Simple Steatosis

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with obesity and metabolic syndrome. The recently discovered hormone adiponectin is produced by adipose tissue, and low plasma adiponectin is considered a key factor in the development of the insulin resistance underlying metabolic syndrome. Animal studies suggest that adiponectin may protect against non-alcoholic steatohepatitis, but direct evidence in humans is lacking. We therefore conducted this study to assess the relationship between plasma adiponectin and nonalcoholic fatty liver disease to explore its role in the pathogenesis of this disease. Design and methods: We measured plasma adiponectin and anthropometric, biochemical, hormonal and metabolic correlates in a group of 17 NAFLD patients with diagnosis confirmed by biopsy, and 20 controls with comparable age, body-mass index and sex. Furthermore we compared plasma adiponectin in patients with simple steatosis and steatohepatitis. Results: Plasma adiponectin was significantly lower in NAFLD patients than controls (5.93±0.45 vs 15.67±1.60 ng/ml). Moreover, NAFLD patients were significantly more insulin resistant while having similar serum leptin. Adiponectin was similar in simple steatosis and in steatohepatitis (6.16±0.78 vs 5.69±0.49 ng/ml). An inverse correlation was observed between adiponectin and homeostatic model assessment (HOMA) of insulin resistance (P = 0.008), while adiponectin did not correlate with serum transaminases and lipid values. Conclusions: These data support a role for low circulating adiponectin in the pathogenesis of NAFLD and confirm the strict association between reduced adiponectin production by adipose tissue, NAFLD and insulin resistance.

scholarly journals Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome

2008 ◽  
Vol 197 (2) ◽  
pp. 189-204 ◽  
Author(s):  
David P Macfarlane ◽  
Shareen Forbes ◽  
Brian R Walker
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Hepatic Insulin Resistance ◽  
Induce Insulin Resistance ◽  
The Metabolic Syndrome

Glucocorticoid hormones constitute an integral component of the response to stress, and many of the manifestations of glucocorticoid excess (Cushing's syndrome) are predictable on the basis of their acute effects to raise blood pressure, induce insulin resistance, increase protein catabolism and elevate plasma glucose. However, it appears to be a paradox that the acute lipolytic effect of glucocorticoids is not manifest in long-term weight loss in humans. The effects of glucocorticoids on glucose metabolism are well characterised, involving impaired peripheral glucose uptake and hepatic insulin resistance, and there is mounting evidence that subtle abnormalities in glucocorticoid concentrations in the plasma and/or in tissue sensitivity to glucocorticoids are important in metabolic syndrome. The effects of glucocorticoids on fatty acid metabolism are less well understood than their influence on glucose metabolism. In this article, we review the literature describing the effects of glucocorticoids on fatty acid metabolism, with particular reference to in vivo human studies. We consider the implications for contrasting acute versus chronic effects of glucocorticoids on fat accumulation, effects in different adipose depots and the potential role of glucocorticoid signalling in the pathogenesis and therapy of metabolic syndrome.

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