Lee Hankyu, Song Jieun, Jung Joo Hyun, Ko Hyuk Wan
College of Pharmacy, Dongguk University, Goyang 10326, Korea.
BMB Rep. 2015 Dec;48(12):647-54. doi: 10.5483/bmbrep.2015.48.12.229.
Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alström syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell's antenna to obesity and type II diabetes.
我们身体系统中的能量平衡是通过平衡能量的摄入和消耗来维持的。破坏平衡系统导致脂肪过度堆积，从而引起超重和肥胖，这正日益成为全球健康问题。对肥胖发病机制的理解主要集中在研究与家族性肥胖类型相关的基因上。最近，一种罕见的人类遗传疾病——纤毛病，将调节细胞器初级纤毛结构和功能的基因作用与代谢紊乱、肥胖和II型糖尿病联系起来。初级纤毛是以微管为基础的毛发状膜结构，缺乏运动性，具有感知环境线索以及在细胞内转导细胞外信号等功能。有趣的是，纤毛病的子类，如巴德-比德尔综合征和阿尔斯特伦综合征，在人类和小鼠模型系统中表现出肥胖和II型糖尿病。此外，对基因小鼠模型系统的研究表明，更多的纤毛基因通过多个调控步骤影响能量平衡，如瘦素和胰岛素的中枢和外周作用。在这篇综述中，我们讨论了初级纤毛与代谢紊乱的最新研究结果，并提出了初级纤毛与瘦素和胰岛素信号通路之间可能的相互作用，这可能会增进我们对细胞的“天线”与肥胖和II型糖尿病之间明确联系的理解。
