Effects of Branch Chain Amino Acids on Glucose Tolerance in Obese Pre-diabetic Subjects

1. BCAA's multiple functions in cells In addition to participating in de novo protein synthesis, Branched-Chain Amino Acids (BCAAs, including leucine, isoleucine, and valine) regulate multiple cellular functions as nutrient signaling. For example, BCAAs regulate insulin and glucagon secretion and thus glucose metabolism1. BCAAs, especially leucine, is one key regulator of mTOR signaling, which is the central component of a complex signaling network of insulin signaling, cell growth, and proliferation. BCAAs also regulate protein synthesis and degradation in various tissues. 2. Impact of BCAA supplemental or BCAA-enriched diet on metabolism In addition to the healthcare utilization of BCAAs for liver disorders and their complications and other diseases, BCAA supplementation is common amongst athletes and fitness professionals to improve muscle building and strength. Meanwhile, BCAA supplementation or BCAA-rich protein diets are often associated with positive effects on body weight and glucose homeostasis1. Increasing dietary uptake of BCAAs improved the parameters associated with obesity and T2DM, such as body composition and glycemia levels. However, these beneficial effects are not conclusive. Moreover, other studies have shown that circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents2. 3. Summary Both beneficial and detrimental effects of BCAA on metabolism have been established and therefore warrants further investigation. In the preliminary study, we found that BCAAs enhanced glucose metabolism in lean mice while they promoted glucose intolerance in obese mice. In lean mice, BCAAs decreased adiposity and enhanced glucose utilization and insulin sensitivity in different tissues. But in obese mice, BCAAs' effects were mediated by impaired insulin signaling in fat tissue.