Monomethyl branched-chain fatty acid mediates amino acid sensing by mTORC1

Animals have developed various nutrient-sensing mechanisms for survival under fluctuating environments. Although extensive cultured cell-based analyses have discovered diverse mediators of amino acid sensing by mTOR, studies using animal models to illustrate intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here we developed a Caenorhabditis elegans model to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid, and downstream glycosphingolipid, that critically mediate overall amino acid sensing by intestinal and neuronal mTORC1 that, in turn, regulates postembryonic development partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may be conserved in mammals. This study uncovers an unexpected amino acid sensing mechanism mediated by a lipid biosynthesis pathway.