N -acyl taurines are endogenous lipid messengers that improve glucose homeostasis

Significance Deletion of fatty acid amide hydrolase (FAAH) in mice results in the concomitant elevation of 2 major types of fatty acid amides, N -acylethanolamines (NAEs) and N -acyl taurines (NATs), as well as obesity, hyperphagia, and insulin resistance. However, the respective contribution of each class of fatty acid amide to these phenotypes is unresolved. Here we employ an engineered variant of FAAH to specifically elevate NATs in vivo and administer the predominant circulating human NAT species to mice, demonstrating that NATs improve insulin sensitivity and augment secretion of the antidiabetic hormone GLP-1. These findings expose a divergent role for FAAH substrates in the regulation of glucose homeostasis, informing future efforts to target fatty acid amide signaling to treat metabolic disease.