AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice
Meric Erikci Ertunc, Bernard P. Kok, William H. Parsons, Justin Wang, Dan Tan, Cynthia J. Donaldson, Antônio F. M. Pinto, Joan Vaughan, Nhi Ngo, Kenneth M. Lum, Cassandra L. Henry, Aundrea R. Coppola, Micah J. Niphakis, Benjamin F. Cravatt, Enrique Sáez, Alan Saghatelian
Abstract
Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.