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

OBJECTIVEObesity 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 METHODSWe 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. RESULTSBCAA 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. CONCLUSIONSOur 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.

Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

“…Improving insulin sensitivity may also ameliorate BCAA metabolism, resulting in reduced diabetes risk. This approach is supported by the well-described reduction of amino acid levels following the administration or secretion of insulin [63,64], by our finding of higher BCAA levels in individuals with a genetic predisposition to insulin resistance, and by the observation of reduced BCAA levels following insulin-sensitising interventions [65–67]. …”

Neuroendocrine adaptations to bariatric surgery

“…These findings suggest BCAAs or their metabolites may contribute to non-weight loss improvements in insulin sensitivity and glucose metabolism (Laferrere et al, 2011). The RYGB specific reduction in BCAAs has been confirmed when compared with AGB and very low calorie diet induced weight loss (Lips et al, 2014). However, in another well conducted study, RYGB and AGB were found to cause the same reduction in circulating BCAAs and their metabolites (Magkos et al, 2013).…”

Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites

“…BCAA deprivation in rodents also improves insulin sensitivity in insulin resistant mice [13]. On the other hand, the rapid increase in insulin sensitivity and improvement in glucose homeostasis following weight loss surgery coincides with reductions in circulating BCAA, AAA, and several AA metabolites [14–16]. In addition, three months of metformin monotherapy has been reported to reduce AAA in patients with T2D [17].…”