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Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice

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Author: Boer, M.A.M. den · Voshol, P.J. · Schröder-van Der Elst, J.P. · Korsheninnikova, E. · Ouwens, D.M. · Kuipers, F. · Havekes, L.M. · Romijn, J.A.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Endocrinology, 10, 147, 4553-4558
Identifier: 239484
doi: doi:10.1210/en.2006-0417
Keywords: Biology · Biomedical Research · Amyloid A protein · fibrinogen · interleukin 10 · protein kinase B · Animal experiment · Calorimetry · Cholesterol blood level · Controlled study · Experimental model · Fatty liver · Feeding · Glucose blood level · Hlucose metabolism · High performance liquid chromatography · Hyperinsulinemia · Insulin sensitivity · Lipid diet · Lipid metabolism · Mouse · Nonhuman · Phosphorylation · Steatosis · Triacylglycerol blood level · Adipose Tissue · Animals · Blood Glucose · Chromatography, Thin Layer · Diet · Dietary Fats · Energy Metabolism · Fibrinogen · Genotype · Glucose · Glucose Clamp Technique · Insulin Resistance · Interleukin-10 · Lipid Metabolism · Lipids · Liver Diseases · Male · Mice · Mice, Inbred C57BL · Mice, Knockout · Phenotype · Serum Amyloid A Protein

Abstract

Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insulin resistance. We compared parameters of glucose and lipid metabolism between IL-10-/- mice and wild-type (wt) mice fed a high-fat diet for 6 wk. This diet has previously been shown to induce steatosis and insulin resistance. After 6 wk on the high-fat diet, no differences in body weight, basal metabolism (measured by indirect calorimetry), or plasma levels of glucose, triglycerides, or cholesterol were observed between IL-10-/- and wt mice. Nonetheless, in IL-10-/- mice, plasma free fatty acid levels were 75% increased compared with wt mice after overnight fasting (P < 0.05). In addition, hepatic triglyceride content was 54% increased in IL-10-/- mice (P < 0.05). During a hyperinsulinemic euglycemic clamp, no differences were observed in whole-body or hepatic insulin sensitivity between both groups. We conclude that basal IL-10 production protects against hepatic steatosis but does not improve hepatic or whole-body insulin sensitivity, during high-fat feeding. Copyright © 2006 by The Endocrine Society. Chemicals / CAS: amyloid A protein, 59165-71-8; fibrinogen, 9001-32-5; protein kinase B, 148640-14-6; Blood Glucose; Dietary Fats; Fibrinogen, 9001-32-5; Glucose, 50-99-7; Interleukin-10, 130068-27-8; Lipids; Serum Amyloid A Protein