Cheung Wai W, Mao Peizhong
Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
ISRN Endocrinol. 2012;2012:536905. doi: 10.5402/2012/536905. Epub 2012 Mar 5.
The prevalence of obesity, which is a heritable trait that arises from the interactions of multiple genes and lifestyle factors, continues to increase worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past several years, various genetic epidemiological approaches have been utilized to identify genetic loci for obesity. Recent evidence suggests that development of obesity involves hormones and neurotransmitters (such as leptin, cocaine- and amphetamine-regulated transcript (CART), and ghrelin) that regulate appetite and energy expenditure. These hormones act on specific centers in the brain that regulate the sensations of satiety. Mutations in these hormones or their receptors can lead to obesity. Aberrant circadian rhythms and biochemical pathways in peripheral organs or tissues have also been implicated in the pathology of obesity. More interestingly, increasing evidence indicates a potential relation between obesity and central nervous system disorders (such as cognitive deficits). This paper discusses recent advances in the field of genetics of obesity with an emphasis on several established loci that influence obesity. These recently identified loci may hold the promise to substantially improve our insights into the pathophysiology of obesity and open up new therapeutic strategies to combat growing obesity epidemic facing the human population today.
肥胖是一种由多种基因和生活方式因素相互作用产生的可遗传特征,在全球范围内其患病率持续上升,引发了严重的健康问题,并给社会带来了沉重的经济负担。在过去几年中,各种遗传流行病学方法已被用于确定肥胖相关的基因位点。最近的证据表明,肥胖的发生涉及调节食欲和能量消耗的激素和神经递质(如瘦素、可卡因和安非他明调节转录物(CART)以及胃饥饿素)。这些激素作用于大脑中调节饱腹感的特定中枢。这些激素或其受体的突变可导致肥胖。外周器官或组织中异常的昼夜节律和生化途径也与肥胖的病理过程有关。更有趣的是,越来越多的证据表明肥胖与中枢神经系统疾病(如认知缺陷)之间存在潜在联系。本文讨论了肥胖遗传学领域的最新进展,重点介绍了几个已确定的影响肥胖的基因位点。这些最近发现的基因位点可能有望大幅增进我们对肥胖病理生理学的理解,并为应对当今人类面临的日益严重的肥胖流行开辟新的治疗策略。