title: Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk.
abstract: Metabolomic profiling of obese individuals revealed altered concentrations of many metabolites, especially branched-chain amino acids (BCAA), possibly linked to altered adipose tissue BCAA catabolism. We tested the hypothesis that some features of this metabolite signature relate closely to visceral obesity and concomitant alterations in cardiometabolic risk factors. We also postulated that alterations in BCAA-catabolizing enzymes are predominant in visceral adipose tissue. Fifty-nine women (BMI 20-41 kg/m(2)) undergoing gynecologic surgery were recruited and characterized for overall and regional adiposity, blood metabolite levels using targeted metabolomics, and cardiometabolic risk factors. Adipose samples (visceral and subcutaneous) were obtained and used for gene expression and Western blot analyses. Obese women had significantly higher circulating BCAA and kynurenine/tryptophan (Kyn/Trp) ratio than lean or overweight women (P < 0.01). Principal component analysis confirmed that factors related to AA and the Kyn/Trp ratio were positively associated with BMI, fat mass, visceral or subcutaneous adipose tissue area, and subcutaneous adipocyte size (P ≤ 0.05). AA-related factor was positively associated with HOMA-IR (P ≤ 0.01). Factors reflecting glycerophospholipids and sphingolipids levels were mostly associated with altered blood lipid concentrations (P ≤ 0.05). Glutamate level was the strongest independent predictor of visceral adipose tissue area (r = 0.46, P < 0.001). Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue than overweight or lean women (P ≤ 0.05). We conclude that among metabolites altered in obesity plasma concentrations of BCAA and the Kyn/Trp ratio are closely related to increased adiposity. Alterations in expression and protein levels of BCAA-catabolizing enzymes are predominant in visceral adipose tissue.
authors: Endocrinology and Nephrology, Centre Hospitalier Universitaire de Quebec, Quebec City, Canada; School of Nutrition, Laval University, Quebec City, Canada; Quebec Heart and Lung Institute, Quebec City, Canada;
authors: Marie Michèle
authors: MM
authors: Boulet
authors: Quebec Heart and Lung Institute, Quebec City, Canada;
authors: Geneviève
authors: G
authors: Chevrier
authors: Quebec Heart and Lung Institute, Quebec City, Canada;
authors: Thomas
authors: T
authors: Grenier-Larouche
authors: Endocrinology and Nephrology, Centre Hospitalier Universitaire de Quebec, Quebec City, Canada;
authors: Mélissa
authors: M
authors: Pelletier
authors: Quebec Heart and Lung Institute, Quebec City, Canada;
authors: Mélanie
authors: M
authors: Nadeau
authors: Helmholtz Zentrum München, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany;
authors: Julia
authors: J
authors: Scarpa
authors: Helmholtz Zentrum München, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany;
authors: Cornelia
authors: C
authors: Prehn
authors: Quebec Heart and Lung Institute, Quebec City, Canada;
authors: André
authors: A
authors: Marette
authors: Helmholtz Zentrum München, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany; and German Center for Diabetes Research, Neuherberg, Germany.
authors: Jerzy
authors: J
authors: Adamski
authors: Endocrinology and Nephrology, Centre Hospitalier Universitaire de Quebec, Quebec City, Canada; School of Nutrition, Laval University, Quebec City, Canada; Quebec Heart and Lung Institute, Quebec City, Canada; andre.tchernof@crchul.ulaval.ca.
authors: André
authors: A
authors: Tchernof
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000473:pathology; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D050218:Body Fat Distribution; D002318:Cardiovascular Diseases / Q000378:metabolism*; D048429:Cell Size; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D055432:Metabolomics; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012307:Risk Factors; D050151:Subcutaneous Fat / Q000378:metabolism; D013851:Thinness / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
chemical_list: D054392:Adipokines; D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D012333:RNA, Messenger; D014280:Triglycerides; D007737:Kynurenine; D014364:Tryptophan; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
keywords: branched-chain amino acids; cardiometabolic risk factors; visceral obesity