Mirjam A Lips1, Jan B Van Klinken2, Vanessa van Harmelen2, Harish K Dharuri2, Peter A C 't Hoen2, Jeroen F J Laros2, Gert-Jan van Ommen2, Ignace M Janssen3, Bert Van Ramshorst4, Bart A Van Wagensveld5, Dingeman J Swank6, Francois Van Dielen7, Adrie Dane8, Amy Harms8, Rob Vreeken8, Thomas Hankemeier8, Johannes W A Smit9, Hanno Pijl9, Ko Willems van Dijk10. 1. Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands m.a.lips@lumc.nl. 2. Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Surgery, Rijnstate Ziekenhuis, Arnhem, the Netherlands. 4. Department of Surgery, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands. 5. Department of Surgery, Sint Lucas Andreas Ziekenhuis, Amsterdam, the Netherlands. 6. Nederlandse Obesitas Kliniek West, Den Haag, the Netherlands. 7. Department of Surgery, Máxima Medisch Centrum, Eindhoven, the Netherlands. 8. Leiden Amsterdam Centre for Drug Research, Netherlands Metabolomics Centre, Leiden, the Netherlands. 9. Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden, the Netherlands. 10. 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.
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. RESEARCH DESIGN AND 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.
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. RESEARCH DESIGN AND 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: R Jokinen; R Rinnankoski-Tuikka; S Kaye; L Saarinen; S Heinonen; M Myöhänen; E Rappou; S Jukarainen; A Rissanen; A Pessia; V Velagapudi; K A Virtanen; E Pirinen; K H Pietiläinen Journal: Int J Obes (Lond) Date: 2017-12-05 Impact factor: 5.095
Authors: Brian A Irving; Rickey E Carter; Mattias Soop; Audrey Weymiller; Husnain Syed; Helen Karakelides; Sumit Bhagra; Kevin R Short; Laura Tatpati; Rocco Barazzoni; K Sreekumaran Nair Journal: Metabolism Date: 2015-01-22 Impact factor: 8.694