Singhal Neel S, Patel Rajesh T, Qi Yong, Lee Yun-Sik, Ahima Rexford S
Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, PA 19104, USA.
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E331-8. doi: 10.1152/ajpendo.00577.2007. Epub 2008 May 27.
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.
抵抗素已与代谢综合征的多个组成部分相关联，包括肥胖、胰岛素抵抗和高脂血症。我们推测抵抗素缺乏会逆转遗传性肥胖中的高脂血症。当喂食标准啮齿动物饲料或高脂饮食时，缺乏抵抗素的C57Bl/6J小鼠[抵抗素基因敲除（RKO）小鼠]的体重和脂肪与野生型小鼠相似。尽管如此，饮食诱导的肥胖RKO小鼠的肝脂肪变性、血清胆固醇和极低密度脂蛋白（VLDL）分泌减少。抵抗素缺乏加剧了ob/ob小鼠的肥胖，但肝脂肪变性明显减轻。此外，ob/ob-RKO小鼠的甘油三酯、胆固醇、胰岛素和葡萄糖水平降低。抵抗素缺乏的抗脂肪变性作用与参与肝脏脂肪生成和VLDL输出的基因表达降低有关。总之，这些结果证明了抵抗素在促进肥胖小鼠肝脂肪变性和高脂血症中起关键作用。
