Submitted on September 6, 2007
Accepted on May 26, 2008
Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin deficient mice
Neel Singhal1, Rajesh T Patel1, Yong Qi1, Yun-Sik Lee, and Rexford S Ahima2*
1 Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
2 Div of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: ahima{at}mail.med.upenn.edu.
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 (Rko) had similar body weight and fat as wild type mice when fed standard rodent chow or high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese (DIO) 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 anti-steatotic 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.
