Genes that make you fat, but keep you healthy.
Genes that make you fat, but keep you healthy.
复制标题
DOI：
10.1111/joim.12827
复制
发表时间：
2018-11
影响因子：
11.1
通讯作者：
Kilpeläinen TO
中科院分区：
文献类型：
--
作者：
Loos RJF;Kilpeläinen TO
肥胖症在全球范围内持续上升，给人们的健康和福祉带来了巨大负担。然而，高达45%的肥胖个体不患有心脏代谢并发症，也被称为代谢健康肥胖（MHO）。同时，高达30%的正常体重个体表现出通常仅见于肥胖个体的心脏代谢风险因素;所谓的代谢性肥胖正常体重（MONW）。除了生活方式因素（体力活动、饮食、吸烟等）和人口统计学因素（年龄、性别、血统）外，已知先天生物学机制也有助于MHO和MONW表型的病因学。动物模型的实验研究表明，脂肪组织和脂肪细胞生物学是关键因素，脂肪组织扩张性、脂肪分布、脂肪形成、脂肪组织血管化、炎症和线粒体功能等机制是将肥胖与心脏代谢合并症分离的主要机制。我们回顾了目前的研究，利用遗传关联数据，以扩大对MHO/MONW表型的生物学的见解。通过对体脂百分比（BF%）的全基因组关联研究，确定了至少四个遗传基因座，其中BF%增加等位基因与对血糖和血脂结果的保护作用相关。对于一些人来说，这种关联是通过对身体脂肪分布的有利影响来介导的。其他旨在表征胰岛素抵抗遗传易感性的研究发现，由于臀部和腿部脂肪积累较少，较高的遗传易感性与较低的总体肥胖相关，这表明脂肪组织中储存脂肪的能力受损可能对代谢有害。虽然这些遗传关联研究已经开始为MHO/MONW表型的生物学提供新的见解，但尚未进行有目的地设计的全基因组关联研究以无假设的方式发现新基因。显然，在这一领域还有很多工作要做，首先是通过基因发现，随后是通过对已鉴定基因的功能跟踪。
Obesity prevalence continues to rise worldwide, posing a substantial burden on people’s health and wellbeing. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also referred to as the metabolically healthy obese (MHO). Concurrently, up to 30% of normal weight individuals demonstrate cardiometabolic risk factors that are typically only seen in obese individuals; the so called metabolically obese normal weight (MONW). Besides lifestyle factors (physical activity, diet, smoking, …) and demographic (age, sex, ancestry) factors, innate biological mechanisms are known to contribute to the etiology of the MHO and MONW phenotypes, as well. Experimental studies in animal models have shown that adipose tissue and adipocyte biology are key players, and mechanisms such as adipose tissue expandability, fat distribution, adipogenesis, vascularization of adipose tissue, inflammation, and mitochondrial function are the main mechanisms that uncouple adiposity from its cardiometabolic comorbidities. We reviewed the current studies that take advantage of genetic association data to expand insights into the biology of MHO/MONW phenotypes. At least four genetic loci were identified through genome-wide association studies for body fat percentage (BF%) of which the BF%-increasing allele was associated with a protective effect on glycemic and lipid outcomes. For some – but not all – this association was mediated through favorable effect on body fat distribution. Other studies that aimed to characterize the genetic susceptibility of insulin resistance, found that a higher genetic susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat in adipose tissue may be metabolically harmful. While these genetic association studies have started to provide new insights into the biology of MHO/MONW phenotypes, purposefully designed genome-wide association studies to discover new genes in a hypothesis-free manner have not yet been performed. Clearly, a lot more work remains to be done in this field, first through gene discovery, and subsequently through functional follow-up of identified genes.
登录
查看更多内容
影响因子：
5.9
作者：
Choi SI;Chung D;Lim JS;Lee MY;Shin JY;Chung CH;Huh JH
通讯作者：
Huh JH
影响因子：
11
作者：
Davies G;Harris SE;Reynolds CA;Payton A;Knight HM;Liewald DC;Lopez LM;Luciano M;Gow AJ;Corley J;Henderson R;Murray C;Pattie A;Fox HC;Redmond P;Lutz MW;Chiba-Falek O;Linnertz C;Saith S;Haggarty P;McNeill G;Ke X;Ollier W;Horan M;Roses AD;Ponting CP;Porteous DJ;Tenesa A;Pickles A;Starr JM;Whalley LJ;Pedersen NL;Pendleton N;Visscher PM;Deary IJ
通讯作者：
Deary IJ
影响因子：
5.8
作者：
Aung, Koko;Lorenzo, Carlos;Haffner, Steven M.
通讯作者：
Haffner, Steven M.
影响因子：
5.8
作者：
Conus, F;Allison, DB;Poehlman, ET
通讯作者：
Poehlman, ET
影响因子：
4.8
作者：
Cariou, B;Capitaine, N;Burnol, AF
通讯作者：
Burnol, AF