Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice |
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Authors: | Singhal Neel S Patel Rajesh T Qi Yong Lee Yun-Sik Ahima Rexford S |
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Institution: | Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, PA 19104, USA. |
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Abstract: | Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol, and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese RKO mice. Resistin deficiency exacerbated obesity in ob/ob mice, but hepatic steatosis was drastically attenuated. Moreover, the levels of triglycerides, cholesterol, insulin, and glucose were reduced in ob/ob-RKO mice. The antisteatotic effect of resistin deficiency was related to reductions in the expression of genes involved in hepatic lipogenesis and VLDL export. Together, these results demonstrate a crucial role of resistin in promoting hepatic steatosis and hyperlipidemia in obese mice. |
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