Several components of the signaling cascade that mediates the HMB-induced increase in human skeletal muscle protein synthesis have been identified "in vivo". Similar to HMB's metabolic precursor, , HMB has been shown to increase protein synthesis in human skeletal muscle via phosphorylation of the mechanistic target of rapamycin (mTOR) and subsequent activation of , which leads to protein biosynthesis in cellular ribosomes via phosphorylation of mTORC1's immediate targets (i.e., the p70S6 kinase and the translation repressor protein 4EBP1). Supplementation with HMB in several non-human animal species has been shown to increase the serum concentration of growth hormone and insulin-like growth factor 1 (IGF-1) via an unknown mechanism, in turn promoting protein synthesis through increased mTOR phosphorylation. Based upon limited clinical evidence in humans, supplemental HMB appears to increase the secretion of growth hormone and IGF-1 in response to resistance exercise.