The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation

Elevated levels of branched-chain amino acids (BCAAs) and their metabolites are strongly positively associated with obesity, insulin resistance, and type 2 diabetes. Bariatric surgery is among the best treatments for weight loss and associated morbidities. Clinical studies have reported that bariatric surgery decreases the circulating levels of BCAAs. The objective of this study was to test the hypothesis that reduced BCAA levels contribute to the metabolic improvements of sustained weight loss and improved glucose tolerance after vertical sleeve gastrectomy (VSG). We find that, as in humans, circulating BCAAs are significantly lower in VSG rats and mice. To increase circulating BCAAs, we tested mice with either increased dietary intake of BCAAs or impaired BCAA catabolism by total body deletion of mitochondrial phosphatase 2C (Pp2cm). Our results show that a decrease in circulating BCAAs is not necessary for sustained body weight loss and improved glucose tolerance after VSG. [Display omitted] •VSG surgery causes reduced levels of circulating branched-chain amino acids (BCAAs)•An increase in dietary BCAAs does not reduce benefits of VSG on weight and glucose•Deletion of Pp2cm blocks VSG’s lowering of BCAAs but does not reduce benefits•BCAAs are markers of VSG benefits but are not a driver of weight loss and glucose levels Increased branched-chain amino acid (BCAA) levels are biomarkers of metabolic disease, and bariatric surgeries reduce BCAA levels. Bozadjieva Kramer et al. show that both dietary and genetic manipulations can block the surgical effect on BCAAs but do not alter potent, beneficial effects on weight loss and glucose tolerance.