title: Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans.
abstract: OBJECTIVE
  Obesity is associated with decreased insulin sensitivity (IS) and elevated plasma branched-chain amino acids (BCAAs). The purpose of this study was to investigate the relationship between BCAA metabolism and IS in overweight (OW) individuals during exercise intervention.
  
  
  METHODS
  Whole-body leucine turnover, IS by hyperinsulinaemic-euglycaemic clamp, and circulating and skeletal muscle amino acids, branched-chain α-keto acids and acylcarnitines were measured in ten healthy controls (Control) and nine OW, untrained, insulin-resistant individuals (OW-Untrained). OW-Untrained then underwent a 6 month aerobic and resistance exercise programme and repeated testing (OW-Trained).
  
  
  RESULTS
  IS was higher in Control vs OW-Untrained and increased significantly following exercise. IS was lower in OW-Trained vs Control expressed relative to body mass, but was not different from Control when normalised to fat-free mass (FFM). Plasma BCAAs and leucine turnover (relative to FFM) were higher in OW-Untrained vs Control, but did not change on average with exercise. Despite this, within individuals, the decrease in molar sum of circulating BCAAs was the best metabolic predictor of improvement in IS. Circulating glycine levels were higher in Control and OW-Trained vs OW-Untrained, and urinary metabolic profiling suggests that exercise induces more efficient elimination of excess acyl groups derived from BCAA and aromatic amino acid (AA) metabolism via formation of urinary glycine adducts.
  
  
  CONCLUSIONS
  A mechanism involving more efficient elimination of excess acyl groups derived from BCAA and aromatic AA metabolism via glycine conjugation in the liver, rather than increased BCAA disposal through oxidation and turnover, may mediate interactions between exercise, BCAA metabolism and IS.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01786941.
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Glynn
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Lucy W
authors.initials: LW
authors.lastname: Piner
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Huffman
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Department of Cardiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Cris A
authors.initials: CA
authors.lastname: Slentz
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Elliot-Penry
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Endocrinology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Hiba
authors.initials: H
authors.lastname: AbouAssi
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: White
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Endocrinology, Duke University Medical Center, Durham, NC, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Olga R
authors.initials: OR
authors.lastname: Ilkayeva
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Endocrinology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: Porter Starr
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Geriatrics, Duke University Medical Center, Durham, NC, USA.|GRECC, Durham VA Medical Center, Durham, NC, USA.
authors.forename: Connie W
authors.initials: CW
authors.lastname: Bales
authors.affiliation: Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.affiliation: The CV and Metabolic Diseases Research Unit, Pfizer, Cambridge, MA, USA.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: Brosnan
authors.affiliation: The CV and Metabolic Diseases Research Unit, Pfizer, Cambridge, MA, USA.
authors.forename: Jeff K
authors.initials: JK
authors.lastname: Trimmer
authors.affiliation: The CV and Metabolic Diseases Research Unit, Pfizer, Cambridge, MA, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Rolph
authors.affiliation: Sarah W. Stedman Nutrition & Metabolism Center, Duke University Medical Center, Durham, NC, USA. Chris.Newgard@dm.duke.edu.|Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA. Chris.Newgard@dm.duke.edu.|Department of Medicine, Duke University Medical Center, Durham, NC, USA. Chris.Newgard@dm.duke.edu.|Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA. Chris.Newgard@dm.duke.edu.|Division of Endocrinology, Duke University Medical Center, Durham, NC, USA. Chris.Newgard@dm.duke.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC, 27701, USA. William.Kraus@dm.duke.edu.|Department of Medicine, Duke University Medical Center, Durham, NC, USA. William.Kraus@dm.duke.edu.|Department of Cardiology, Duke University Medical Center, Durham, NC, USA. William.Kraus@dm.duke.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
mesh_terms: D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D015309:Glucose Clamp Technique; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D050177:Overweight / Q000378:metabolism* / Q000628:therapy; D055070:Resistance Training; D016896:Treatment Outcome
chemical_list: D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D005998:Glycine
keywords: Branched-chain amino acids; Exercise; Insulin resistance; Metabolomics; Obesity; Protein