کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5946824 | 1172362 | 2014 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Cholesterol-induced hepatic inflammation does not contribute to the development of insulin resistance in male LDL receptor knockout mice Cholesterol-induced hepatic inflammation does not contribute to the development of insulin resistance in male LDL receptor knockout mice](/preview/png/5946824.png)
- Kupffer cell-driven hepatic inflammation in insulin resistance was studied.
- We used Ldlrâ/â mice fed a 0.2% cholesterol-rich high-fat diet for 2 and 15 weeks.
- Hepatic inflammation with normal insulin sensitivity at 2 weeks of HFC diet in mice.
- Insulin resistance is not exacerbated in obese Ldlrâ/â mice at 15 weeks of HFC diet.
- Our data question a role for Kupffer cells in control of insulin sensitivity.
ObjectiveIt is generally assumed that hepatic inflammation in obesity is linked to the pathogenesis of insulin resistance. Several recent studies have shed doubt on this view, which questions the causality of this association. This study focuses on Kupffer cell-mediated hepatic inflammation as a possible driver of insulin resistance in the absence and presence of obesity.MethodsWe used male mice deficient for the low-density lipoprotein receptor (Ldlrâ/â) and susceptible to cholesterol-induced hepatic inflammation. Whole body and hepatic insulin resistance was measured in mice fed 4 diets for 2 and 15 weeks, i.e., chow, high-fat (HF), HF-cholesterol (HFC; 0.2% cholesterol) and HF without cholesterol (HFnC). Biochemical parameters in plasma and liver were measured and inflammation was determined using immunohistochemistry and RT-PCR.ResultsAt 2 weeks, we did not find significant metabolic effects in either diet group, except for the mice fed a HFC diet which showed pronounced hepatic inflammation (p < 0.05) but normal insulin sensitivity. At 15 weeks, a significant increase in insulin levels, HOMA-IR, and hepatic insulin resistance was observed in mice fed a HFC, HFnC, and HF diet compared to chow-fed mice (p < 0.05). Regardless of the level of hepatic inflammation (HFC > HF, HFnC; p < 0.05) insulin resistance in mice fed HFC was no worse compared to mice on a HFnC and HF diet.ConclusionThese data show that cholesterol-induced hepatic inflammation does not contribute to the development of insulin resistance in male Ldlrâ/â mice. This study suggests that Kupffer cell-driven hepatic inflammation is a consequence, not a cause, of metabolic dysfunction in obesity.
Journal: Atherosclerosis - Volume 232, Issue 2, February 2014, Pages 390-396