Palmitoyl serinol is a gut microbe-derived agonist of G protein-coupled receptor 119 (GPR119) and a stable derivative of 2-palmitoyl glycerol, an endogenous fatty acid ester that potentiates the signaling and in vivo activity induced by the endocannabinoid 2-arachidonoyl glycerol.^1,2,3,4 It increases cAMP levels in HEK293 cells expressing GPR119 (EC50 = 9 µM).¹ Palmitoyl serinol (25 µM) reduces IL-4-induced decreases in the levels of long-chain fatty acid-containing ceramides in HaCaT keratinocytes, an effect that can be blocked by the cannabinoid receptor 1 (CB1) antagonist AM-251.5 It also binds to PKCζ and induces apoptosis in F-11 neuroblastoma cells, an effect that can be blocked by the PKCζ inhibitor Gö 6983.6 Portal circulation plasma levels of palmitoyl serinol, among other N-acyl amides, are increased under fed and fasted conditions in mice monocolonized with E. coli expressing G. haemolysans M34 N-acyl synthase (nas) and housed under gnotobiotic conditions.⁷