Obesity Research Unit, Division of Internal Medicine and Department of Psychiatry, Helsinki University Central Hospital, Department of Medicine, Helsinki, Finland.
Int J Obes (Lond). 2012 Aug;36(8):1017-24. doi: 10.1038/ijo.2011.192. Epub 2011 Oct 11.
Obesity is a genetically complex disorder that produces a myriad of health problems. Most of the recognized complications of obesity are not only strongly influenced by lifestyle factors, but also present with independent genetic predispositions that are notoriously difficult to disentangle in humans. Most studies on the causes and consequences of acquired obesity are encumbered by the incomplete ability to control for genetic influences. However, utilizing a unique experiment of nature, namely monozygotic twins (MZ) discordant for obesity as 'clonal controls' of obese and non-obese individuals has enabled the fine characterization of the effects and possible antecedents of acquired obesity while controlling for the genetic background, as well as pointed to novel obesity predisposing candidate genes. This review is a distillation of the findings from more than 10 years of research done in an exceptionally well-characterized collection of MZ and dizygotic (DZ) twins, based on the Finnish Twin Cohorts. Topics covered include the nature of development of obesity from the childhood onwards, the role of exercise in modifying the genetic susceptibility, the resulting inflammatory, prediabetic and preatherosclerotic changes in whole body and adipose tissue physiology, as well as the newest insights provided by the omics revolution.
肥胖是一种遗传复杂的疾病，会导致多种健康问题。肥胖的大多数公认并发症不仅受到生活方式因素的强烈影响，而且还具有独立的遗传易感性，这在人类中很难理清。大多数关于获得性肥胖的原因和后果的研究都受到不完全控制遗传影响的能力的限制。然而，利用一种独特的自然实验，即肥胖不一致的同卵双胞胎（MZ）作为肥胖和非肥胖个体的“克隆对照”，可以在控制遗传背景的同时，对获得性肥胖的影响和可能的前兆进行精细描述，并指出新的肥胖易感候选基因。这篇综述是基于芬兰双胞胎队列对 10 多年来对一组特征非常明确的 MZ 和异卵双胞胎（DZ）进行的研究结果的提炼。涵盖的主题包括肥胖从儿童期开始的发展性质、运动在改变遗传易感性方面的作用、全身和脂肪组织生理学中由此产生的炎症、糖尿病前期和动脉粥样硬化前变化，以及组学革命提供的最新见解。
