title: System model network for adipose tissue signatures related to weight changes in response to calorie restriction and subsequent weight maintenance.
abstract: Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Departments of Clinical Biochemistry and Nutrition, Toulouse, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Montastier
authors.affiliation: INRA, UR875 MIAT, Castanet Tolosan, France; Statistique, Analyse, Modélisation Multidisciplinaire (SAMM), Université Paris 1, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villa-Vialaneix
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Departments of Clinical Biochemistry and Nutrition, Toulouse, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Caspar-Bauguil
authors.affiliation: Institute of Endocrinology, Obesity Management Centre, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Hlavaty
authors.affiliation: Fourth Department of Internal Medicine, 1st Medical School, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Tvrzicka
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gonzalez
authors.affiliation: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Toulouse University Hospitals, Departments of Clinical Biochemistry and Nutrition, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.affiliation: Institute of Endocrinology, Obesity Management Centre, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Kunesova
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D031204:Caloric Restriction; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D015431:Weight Loss / Q000235:genetics* / Q000502:physiology*; D055815:Young Adult