Cell Metabolism:肥胖致心脏病分子机理揭晓

2010-11-04 00:00 · wythe

肥胖会对心脏造成一定负担。美国一项新研究发现肥胖症和心脏病之间的“分子纽带”,即一种特殊的蛋白质分子会影响脂肪在心脏部位的堆积。 美国桑福德-伯纳姆医学研究所研究人员在新一期《细胞-代谢》杂志上介绍说,他们以果蝇为模型研究发现,这种名为TOR的蛋白质分子可以控制脂肪在心脏部位的

肥胖会对心脏造成一定负担。美国一项新研究发现肥胖症和心脏病之间的“分子纽带”,即一种特殊的蛋白质分子会影响脂肪在心脏部位的堆积。

美国桑福德-伯纳姆医学研究所研究人员在新一期《细胞-代谢》杂志上介绍说,他们以果蝇为模型研究发现,这种名为TOR的蛋白质分子可以控制脂肪在心脏部位的堆积。如果对肥胖果蝇体内的该蛋白质进行调控,就可以使得肥胖果蝇的心脏免受脂肪堆积的损害,有效预防心脏病。

研究人员说,果蝇是研究心脏疾病的理想模型,因为果蝇心脏发育的基本分子机理与脊椎动物十分相似。实验过程中,研究人员用高脂肪的椰子油喂食果蝇,使其变得肥胖,而且出现了与人类肥胖症患者类似的某些症状,如心脏机能失调。

然后,研究人员通过调节果蝇的TOR蛋白质水平发现,当该蛋白质的水平受到抑制时,一种负责分解脂肪的酶的活性就会增强,果蝇心脏部位的脂肪堆积就会减少。这些肥胖果蝇的心脏功能就会得到改善,从而减少患心脏病的几率。

研究人员称,不管是抑制果蝇整个体内的TOR蛋白质水平,还是单纯抑制果蝇脂肪组织或心脏细胞内的TOR蛋白质水平,都能起到同样的保护心脏的作用。这一研究成果将有助于研究人员对肥胖症诱发心脏病等问题进行干预。(


推荐英文摘要:

Cell Metabolism 10.1016/j.cmet.2010.09.014

High-Fat-Diet-Induced Obesity and Heart Dysfunction Are Regulated by the TOR Pathway in Drosophila

Ryan T. Birse, Joan Choi, Kathryn Reardon, Jessica Rodriguez, Suzanne Graham, Soda Diop, Karen Ocorr, Rolf Bodmer, Sean Oldham

High-fat-diet (HFD)-induced obesity is a major contributor to diabetes and cardiovascular disease, but the underlying genetic mechanisms are poorly understood. Here, we use Drosophila to test the hypothesis that HFD-induced obesity and associated cardiac complications have early evolutionary origins involving nutrient-sensing signal transduction pathways. We find that HFD-fed flies exhibit increased triglyceride (TG) fat and alterations in insulin/glucose homeostasis, similar to mammalian responses. A HFD also causes cardiac lipid accumulation, reduced cardiac contractility, conduction blocks, and severe structural pathologies, reminiscent of diabetic cardiomyopathies. Remarkably, these metabolic and cardiotoxic phenotypes elicited by HFD are blocked by inhibiting insulin-TOR signaling. Moreover, reducing insulin-TOR activity (by expressing TSC1-2, 4EBP or FOXO), or increasing lipase expression―only within the myocardium―suffices to efficiently alleviate cardiac fat accumulation and dysfunction induced by HFD. We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function.

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