Fam172a deletion in brown adipose tissue protects against HFD-induced obesity by activating the BDH1-BHB pathway

Family with sequence similarity 172 member A (FAM172A) protein acts as a key physiological repressor of brown adipose tissue (BAT) activity that plays a key role in energy metabolism. Its expression in BAT is suppressed by cold and other adrenergic stimulators. Mechanistically, FAM172A inhibits BAT activity and thermogenesis, in part, by binding to 3-hydroxybutyrate dehydrogenase 1 (BDH1), which subsequently affects the levels of beta-hydroxybutyrate (BHB), a ketone body metabolite closely involved in adipose mitochondrial biogenesis. RNA-binding protein immunoprecipitation (RIP)-sequencing was performed to identify the possible mRNAs that bind to the FAM172A protein in brown adipose tissue under cold exposure.