title: Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.
abstract: Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3), which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.
authors.affiliation: Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tulika
authors.initials: T
authors.lastname: Arora
authors.affiliation: VTT Technical Research Centre of Finland, Espoo, Finland; Metabolomics Unit, Institute for Molecular Medicine Finland FIMM, Helsinki, Finland.
authors.forename: Vidya
authors.initials: V
authors.lastname: Velagapudi
authors.affiliation: Department of Bariatric Surgery, Musgrove Park Hospital, Taunton, United Kingdom.
authors.forename: Dimitri J
authors.initials: DJ
authors.lastname: Pournaras
authors.affiliation: Department of Bariatric Surgery, Musgrove Park Hospital, Taunton, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Welbourn
authors.affiliation: Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Gastrosurgical Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carel W
authors.initials: CW
authors.lastname: le Roux
authors.affiliation: VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
authors.affiliation: Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D002210:Caprylates / Q000097:blood; D003652:Decanoic Acids / Q000097:blood; D003920:Diabetes Mellitus / Q000473:pathology / Q000601:surgery; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism* / Q000601:surgery; D013109:Sphingomyelins / Q000097:blood; D014280:Triglycerides / Q000378:metabolism*; D015431:Weight Loss
chemical_list: D000596:Amino Acids; D002210:Caprylates; D003652:Decanoic Acids; D005227:Fatty Acids; D013109:Sphingomyelins; D014280:Triglycerides; C031492:octanoic acid