title: Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health.
abstract: Abdominal obesity is associated with increased risk of type 2 diabetes (T2D) and cardiovascular disease. The aim of this study was to assess whether metabolomic markers of T2D and blood pressure (BP) act on these traits via visceral fat (VF) mass.
  
  
  
  Metabolomic profiling of 280 fasting plasma metabolites was conducted on 2,401 women from TwinsUK. The overlap was assessed between published metabolites associated with T2D, insulin resistance, or BP and those that were identified to be associated with VF (after adjustment for covariates) measured by dual-energy X-ray absorptiometry.
  
  
  
  In addition to glucose, six metabolites were strongly associated with both VF mass and T2D: lactate and branched-chain amino acids, all of them related to metabolism and the tricarboxylic acid cycle; on average, 38.5% of their association with insulin resistance was mediated by their association with VF mass. Five metabolites were associated with BP and VF mass including the inflammation-associated peptide HWESASXX, the steroid hormone androstenedione, lactate, and palmitate. On average, 29% of their effect on BP was mediated by their association with VF mass.
  
  
  
  Little overlap was found between the metabolites associated with BP and those associated with insulin resistance via VF mass.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Migaud
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Glastonbury
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Beaumont
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Nikolaou
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: Kerrin S
authors.initials: KS
authors.lastname: Small
authors.affiliation: Pfizer Worldwide Research and Development, Clinical Research Statistics, Groton, Connecticut, USA.
authors.forename: Mary Julia
authors.initials: MJ
authors.lastname: Brosnan
authors.affiliation: Metabolon, Inc., Durham, North Carolina, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.|Academic Rheumatology Clinical Sciences Building, Nottingham City Hospital, Nottingham, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D002952:Citric Acid Cycle; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D016014:Linear Models; D024821:Metabolic Syndrome / Q000503:physiopathology*; D055432:Metabolomics; D008875:Middle Aged
chemical_list: D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D019344:Lactic Acid