Vidal, H. (Hubert)
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- Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake(American Society for Nutrition, 2010) Martinez, J.A. (José Alfredo); Saris, W.H.M. (Wim H. M.); Viguerie, N. (N.); Wang, P. (Ping); Vidal, H. (Hubert); Mutch, D.M. (David M.); Jebb, S.A. (Susan A.); Larsen, T.M. (Thomas M.); Langin, D. (D.); Handjieva-Darlenska, T. (Teodora); Babalis, D. (D.); Pfeiffer, A.F. (A.F.); Astrup, A. (Arne); Clement, K. (K.); Roussel, B. (B.); Debard, C. (C.); Holst, C. (C.); Kalouskova, P. (P.); Combes, M. (M.); Marquez-Quiñones, A. (A.); Mariman, E.C. (E.C.)BACKGROUND: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. OBJECTIVE: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. DESIGN: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. RESULTS: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. CONCLUSIONS: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control.
- Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women.(Endocrine Society, 2008) Martinez, J.A. (José Alfredo); Saris, W.H.M. (Wim H. M.); Viguerie, N. (N.); Vidal, H. (Hubert); Klimcakova, E. (E.); Sørensen, T.I.A (Thorkild I. A.); Langin, D. (D.); Clement, K. (K.); Arner, P. (P.); Taylor, M. (Moira); Capel, F. (F.); Vega, N. (Nathalie); Holst, C. (C.); Oppert, J.M. (Jean M.); Dejean, S. (S.)CONTEXT: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. OBJECTIVE: We investigated adipose tissue gene expression from human obese women according to energy deficit and the fat and carbohydrate content of the diet. DESIGN AND SETTING: Obese subjects recruited among eight European clinical centers were followed up 10 wk of either a low-fat (high carbohydrate) or a moderate-fat (low carbohydrate) hypoenergetic diet. SUBJECTS: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. MAIN OUTCOME MEASURE: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24,469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. RESULTS: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. One thousand genes were regulated by energy restriction. We validated an effect of the fat to carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA, and GABARAPL2) with increased expression during the moderate-fat diet. CONCLUSIONS: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response.
- Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation(Public Library of Science, 2012) Martinez, J.A. (José Alfredo); Saris, W.H.M. (Wim H. M.); Valle, C. (Carine); Montastier, E. (E.); Viguerie, N. (N.); Vidal, H. (Hubert); Maoret, J.J. (J.J.); Villa-Vialaneix, N. (N.); Langin, D. (D.); Astrup, A. (Arne); Clement, K. (K.); Roussel, B. (B.); Iacovoni, J.S. (J. S.); Holst, C. (C.); Hager, J. (Jörg); Combes, M. (M.)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.