UC San Diego

A recently discovered class of endogenous lipids called fatty acid esters of hydroxy fatty acids (FAHFAs) display potent anti-diabetic and anti-inflammatory effects. This leads to the question of how these FAHFAs are regulated in vivo.

My thesis work focused on understanding how FAHFAs are biochemically degraded in an animal model. Prior to my work, androgen induced gene 1 (AIG1) and androgen-dependent TFPI regulating protein (ADTRP) were discovered as FAHFA hydrolases and I endeavored to identify Drosophila melanogaster orthologs to provide an additional model to study FAHFA regulation. First, I confirmed that FAHFAs are present in flies, suggesting this is a well conserved lipid class. Conservation analysis revealed two putative FAHFA hydrolases, CG3625b and CG11601, in the Drosophila melanogaster genome. Like AIG1 and ADTRP, CG3625b and CG11601 have a conserved active site threonine, and testing the biochemical activity of these proteins demonstrated that CG3625b and CG11601 are FAHFA hydrolases. The results show that D. melanogaster can be used as a possible animal model to further elucidate how FAHFAs are physiologically regulated.