为何2型糖尿病药物会使患者变得肥胖？

  近日，来自美国乔治亚州立大学(Georgia State University)等处的研究人员通过研究表明，用于治疗2型糖尿病患者的药物或可激活大脑细胞的传感器从而增加个体的饥饿感，并且引发服药患者变胖，相关研究刊登于国际杂志The Journal of Neuroscience上，该研究描述了一种新方法或可帮助解释为何服用治疗2型糖尿病药物的患者会变胖。

  2型糖尿病是一种常见类型的糖尿病，其影响着95%糖尿病患者的健康，1型或2型糖尿病患者机体中往往血糖含量较高，2型糖尿病更易在中老年人及过重个体机体中发生；文章中，研究者发现大脑中的传感器或可检测游离循环的能量，从而来帮助使用位于大脑细胞中的糖类来控制个体的饮食行为，许多糖尿病患者会服用诸如噻唑烷二酮类等（TZDs）的抗糖尿病药物，而这种药物可以特异性地激活大脑传感器。

  研究者Johnny Garretson说道，我们在刺激饥饿的细胞中发现了过氧化物酶体增生物激活受体γ（PPARγ）传感器，比如在刺鼠色蛋白相关蛋白（AgRP）的细胞中，AgRP细胞位于大脑海马体的底部位置；激活PPARγ传感器就会诱发食物的储藏、摄入并且产生更多的AgRP，当AgRP细胞被激活后，动物就会立马变得饥饿起来，而这些细胞具有一定潜力，它们会促进啮齿类动物从睡眠中醒来去进食。

  TZDs可以帮助治疗胰岛素耐受性，从而促进机体胰岛素正常工作，使得机体血糖的水平被控制住，而且促使细胞获取其所应得的能量。摄入TZDs的患者会变得非常饥饿，因此他们需要获取更多的能量，当患者服药时就会激活大量的特殊受体，研究人员认为这些受体可以通过一定的机制来控制机体的营养补给；研究者发现，激活这些特殊受体可以促进啮齿类动物进食量增加并且可以使其在随后的时间段里储存更多的食物，而与此同似乎阻断这些受体则会使得动物的进食量下降以及储存食物减少。

  最后研究者指出，本文研究揭示了为何2型糖尿会变得肥胖，为后期进行更为深入的研究来开发2型糖尿病的新型预防措施和靶向疗法提供了一定的希望和帮助。（转化医学网360zhyx.com）

  以上为转化医学网原创翻译整理，如需转载，请联系 info@360zhyx.com
转化医学网推荐的原文摘要：

Peroxisome Proliferator-Activated Receptor γ Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus
Journal of Neuroscience doi:10.1523/JNEUROSCI.2129-14.2015
John T. Garretson1,3, Brett J.W. Teubner2, Kevin L. Grove4, Almira Vazdarjanova5,6, Vitaly Ryu2,3, and Timothy J. Bartness1,2,3
Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide; PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPARγ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPARγ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors.