title: Roux-en-Y gastric bypass surgery, but not calorie restriction, reduces plasma branched-chain amino acids in obese women independent of weight loss or the presence of type 2 diabetes.
abstract: OBJECTIVE
  Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels.
  
  
  METHODS
  We included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention.
  
  
  RESULTS
  BCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced.
  
  
  CONCLUSIONS
  Our data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects.
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands m.a.lips@lumc.nl.
authors.forename: Mirjam A
authors.initials: MA
authors.lastname: Lips
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Van Klinken
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Harmelen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Harish K
authors.initials: HK
authors.lastname: Dharuri
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jeroen F J
authors.initials: JF
authors.lastname: Laros
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: van Ommen
authors.affiliation: Department of Surgery, Rijnstate Ziekenhuis, Arnhem, the Netherlands.
authors.forename: Ignace M
authors.initials: IM
authors.lastname: Janssen
authors.affiliation: Department of Surgery, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Van Ramshorst
authors.affiliation: Department of Surgery, Sint Lucas Andreas Ziekenhuis, Amsterdam, the Netherlands.
authors.forename: Bart A
authors.initials: BA
authors.lastname: Van Wagensveld
authors.affiliation: Nederlandse Obesitas Kliniek West, Den Haag, the Netherlands.
authors.forename: Dingeman J
authors.initials: DJ
authors.lastname: Swank
authors.affiliation: Department of Surgery, Máxima Medisch Centrum, Eindhoven, the Netherlands.
authors.forename: Francois
authors.initials: F
authors.lastname: Van Dielen
authors.affiliation: Leiden Amsterdam Centre for Drug Research, Netherlands Metabolomics Centre, Leiden, the Netherlands.
authors.forename: Adrie
authors.initials: A
authors.lastname: Dane
authors.affiliation: Leiden Amsterdam Centre for Drug Research, Netherlands Metabolomics Centre, Leiden, the Netherlands.
authors.forename: Amy
authors.initials: A
authors.lastname: Harms
authors.affiliation: Leiden Amsterdam Centre for Drug Research, Netherlands Metabolomics Centre, Leiden, the Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Vreeken
authors.affiliation: Leiden Amsterdam Centre for Drug Research, Netherlands Metabolomics Centre, Leiden, the Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands.
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands.
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands.
authors.forename: Ko
authors.initials: K
authors.lastname: Willems van Dijk
mesh_terms: D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood*; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D015536:Down-Regulation; D005260:Female; D015390:Gastric Bypass; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000178:diet therapy / Q000601:surgery; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000178:diet therapy / Q000601:surgery*; D015431:Weight Loss / Q000502:physiology*
chemical_list: D000597:Amino Acids, Branched-Chain