9.B.287. The Fat Storage-inducing Transmembrane Protein 2 (FIT2) Family
FIT2 aids in partitioning of cellular triacylglycerol into lipid droplets. A genome-wide association study reported the FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations. Mice with adipose tissue (AT)-specific FIT2 knockout exhibited lipodystrophic features, with reduced AT mass, insulin resistance, and greater inflammation in AT when fed a high-fat diet. Agrawal et al. 2018 found FIT2 protein abundance is lower in subcutaneous and omental AT obtained from patients with T2DM compared with nondiabetic control subjects. Partial loss of FIT2 protein in primary human adipocytes attenuated their lipid storage capacity and induced insulin resistance. After palmitate treatment, triacylglycerol accumulation, insulin-induced Akt (Ser-473) phosphorylation, and insulin-stimulated glucose uptake were significantly reduced in FIT2 knockdown adipocytes compared with control cells. FIT2 is associated with T2DM in humans and plays an integral role in maintaining metabolically healthy AT function (Agrawal et al. 2018).