title: Linking diet, physical activity, cardiorespiratory fitness and obesity to serum metabolite networks: findings from a population-based study.
abstract: OBJECTIVE
  It is not yet resolved how lifestyle factors and intermediate phenotypes interrelate with metabolic pathways. We aimed to investigate the associations between diet, physical activity, cardiorespiratory fitness and obesity with serum metabolite networks in a population-based study.
  
  
  METHODS
  The present study included 2380 participants of a randomly drawn subcohort of the European Prospective Investigation into Cancer and Nutrition-Potsdam. Targeted metabolomics was used to measure 127 serum metabolites. Additional data were available including anthropometric measurements, dietary assessment including intake of whole-grain bread, coffee and cake and cookies by food frequency questionnaire, and objectively measured physical activity energy expenditure and cardiorespiratory fitness in a subsample of 100 participants. In a data-driven approach, Gaussian graphical modeling was used to draw metabolite networks and depict relevant associations between exposures and serum metabolites. In addition, the relationship of different exposure metabolite networks was estimated.
  
  
  RESULTS
  In the serum metabolite network, the different metabolite classes could be separated. There was a big group of phospholipids and acylcarnitines, a group of amino acids and C6-sugar. Amino acids were particularly positively associated with cardiorespiratory fitness and physical activity. C6-sugar and acylcarnitines were positively associated with obesity and inversely with intake of whole-grain bread. Phospholipids showed opposite associations with obesity and coffee intake. Metabolite networks of coffee intake and obesity were strongly inversely correlated (body mass index (BMI): r = -0.57 and waist circumference: r = -0.59). A strong positive correlation was observed between metabolite networks of BMI and waist circumference (r = 0.99), as well as the metabolite networks of cake and cookie intake with cardiorespiratory fitness and intake of whole-grain bread (r = 0.52 and r = 0.50; respectively).
  
  
  CONCLUSIONS
  Lifestyle factors and phenotypes seem to interrelate in various metabolic pathways. A possible protective effect of coffee could be mediated via counterbalance of pathways of obesity involving hepatic phospholipids. Experimental studies should validate the biological mechanisms.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Floegel
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wientzek
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bachlechner
authors.affiliation: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jacobs
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Drogan
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krumsiek
authors.affiliation: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: M B
authors.initials: MB
authors.lastname: Schulze
authors.affiliation: Molecular Epidemiology Group, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Berlin-Buch, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Pischon
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Boeing
mesh_terms: D000596:Amino Acids / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002241:Carbohydrates / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D003069:Coffee; D004032:Diet; D004734:Energy Metabolism; D015444:Exercise; D005247:Feeding Behavior; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008019:Life Style; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D010743:Phospholipids / Q000097:blood; D010809:Physical Fitness; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D055105:Waist Circumference
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D002241:Carbohydrates; D003069:Coffee; D010743:Phospholipids; C116917:acylcarnitine; D002331:Carnitine