Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice.
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.
den Boer
Marion A M
MA
Department of Endocrinology and Metabolism, Leiden University Medical Center, C4-R, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. A.M.den_Boer@lumc.nl
Voshol
Peter J
PJ
Schröder-van der Elst
Janny P
JP
Korsheninnikova
Elena
E
Ouwens
D Margriet
DM
Kuipers
Folkert
F
Havekes
Louis M
LM
Romijn
Johannes A
JA
D000273:Adipose Tissue / Q000254:growth & development / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007333:Insulin Resistance / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008107:Liver Diseases / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D000685:Serum Amyloid A Protein / Q000378:metabolism
D001786:Blood Glucose; D004041:Dietary Fats; D008055:Lipids; D000685:Serum Amyloid A Protein; D016753:Interleukin-10; D005340:Fibrinogen; D005947:Glucose