Figlewicz Dianne P, Zavosh Aryana, Sexton Timothy, Neumaier John F
Metabolism/Endocrinology, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E1004-10. doi: 10.1152/ajpendo.00427.2003. Epub 2004 Jan 28.
The central nervous system (CNS) protein "tub" has been identified from the genetically obese "tubby" mouse. Although the native function of tub in situ is not understood, cell-based studies suggest that one of its roles may be as an intracellular signaling target for insulin. In normal animals, insulin acts at the hypothalamic arcuate nucleus (ARC) to regulate energy balance. Here we used a Herpes Simplex viral expression system to evaluate whether tub overexpression in the ARC of normal rats enhances this action of insulin. In chow-fed rats, tub overexpression had no effect on insulin action. In rats fed a high-fat diet snack in addition to chow, simulating the diet of Westernized societies, the body weight regulatory action of insulin was impaired, and tub overexpression further impaired insulin action. Thus an excess of tub at the ARC does not enhance the in vivo effectiveness of insulin and is not able to compensate for the "downstream" consequences of a high-fat diet to impair CNS body weight regulatory mechanisms.
中枢神经系统（CNS）蛋白“tub”是从遗传性肥胖的“tubby”小鼠中鉴定出来的。尽管tub在原位的天然功能尚不清楚，但基于细胞的研究表明，它的作用之一可能是作为胰岛素的细胞内信号传导靶点。在正常动物中，胰岛素作用于下丘脑弓状核（ARC）以调节能量平衡。在此，我们使用单纯疱疹病毒表达系统来评估正常大鼠ARC中tub的过表达是否会增强胰岛素的这种作用。在喂食普通饲料的大鼠中，tub过表达对胰岛素作用没有影响。在除普通饲料外还喂食高脂肪饮食零食的大鼠中，模拟西方化社会的饮食，胰岛素的体重调节作用受损，而tub过表达进一步损害了胰岛素作用。因此，ARC中tub过量并不会增强胰岛素在体内的有效性，也无法补偿高脂肪饮食对中枢神经系统体重调节机制的“下游”损害后果。
