In the physiological context of overnutrition and low IGF-1 levels, as found in our obese subjects, circulating branched-chain amino acids (BCAA) rise, leading to increased flux of these amino acids through their catabolic pathways. We detected changes in several of the intermediary metabolites of the BCAA catabolic pathway in obese subjects, as indicated by the symbol *. A consequence of increased BCAA levels is the activation of the mTOR/S6K1 kinase pathway and phosphorylation of IRS-1 on multiple serines, contributing to insulin resistance. In addition, increased BCAA catabolic flux may contribute to increased gluconeogenesis and glucose intolerance via glutamate transamination to alanine.