Inserm, UMR1048, Obesity Research Laboratory, Team 4, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
PLoS Genet. 2012 Sep;8(9):e1002959. doi: 10.1371/journal.pgen.1002959. Epub 2012 Sep 27.
Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases.
体重控制饮食有利于改善代谢综合征的参数，并延缓糖尿病并发症的发生。脂肪组织（AT）的适应性变化可能对全身反应产生深远影响，因为 AT 是饮食干预的关键靶点。因此，确定控制 AT 适应性的环境和个体因素至关重要。在这里，根据肥胖和体重变化选择了 271 个转录本的表达，在 515 名个体中进行了测定，这些个体在 8 周低热量饮食诱导的体重减轻之前、之后和 26 周随意体重维持饮食之后。对于 175 个基因，在热量限制和体重维持阶段观察到相反的调节，而与体重变化无关。代谢和免疫基因显示出相反的谱。在饮食干预期间，基于网络的分析显示，参与从头脂肪生成的基因表达与代谢综合征的成分之间存在强烈的相互联系。性别对 88 个转录本的 AT 表达有明显影响，这种影响在整个饮食干预期间以及在控制脂肪量后仍然存在。在女性中，体重指数对一部分基因表达的影响在饮食干预期间仍然存在。有 22 个基因显示出男女共有的代谢综合征特征。顺式信号对 AT 基因表达的遗传控制观察到 46 个基因。饮食干预、性别和顺式遗传变异独立控制 AT 基因表达。这些分析有助于理解控制人类 AT 基因表达的环境和个体因素的相对重要性，因此可能有助于制定旨在改善代谢疾病中 AT 功能的策略。
