title: Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation.
abstract: 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.
authors.affiliation: Inserm, UMR1048, Obesity Research Laboratory, Team 4, I2MC, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Emilie
authors.initials: E
authors.lastname: Montastier
authors.forename: Jean-José
authors.initials: JJ
authors.lastname: Maoret
authors.forename: Balbine
authors.initials: B
authors.lastname: Roussel
authors.forename: Marion
authors.initials: M
authors.lastname: Combes
authors.forename: Carine
authors.initials: C
authors.lastname: Valle
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villa-Vialaneix
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Jorg
authors.initials: J
authors.lastname: Hager
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D015992:Body Mass Index; D031204:Caloric Restriction; D002149:Energy Intake / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D015431:Weight Loss