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Submitted on March 31, 2006
Accepted on May 10, 2006
Dept. of Endocrinology and Metabolism, LUMC, Dept. of Molecular Cell Biology, LUMC, Leiden, Dept. of Pediatrics, University Medical Center Groningen, Groningen, Dept. of Cardiology, Leiden University Medical Center, Leiden, Netherlands; TNO Quality of Life, Leiden, Netherlands
* To whom correspondence should be addressed. E-mail: A.M.den Boer{at}lumc.nl.
Several studies have demonstrated an association in humans between plasma levels or production capacity of the anti-inflammatory 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 weeks. This diet has previously been shown to induce steatosis and insulin resistance. After 6 weeks on the high fat diet no differences in bodyweight, basal metabolism (measured by indirect calorimetry) and plasma levels of glucose, triglycerides (TG) 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 TG 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.
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