Fat storage‐inducing Transmembrane Protein 2 adipose tissue deficiency results in decreased adipose tissue mass

Abstract

Adipose tissue serves as the main storage depot of neutral lipids in cytosolic lipid droplets. We recently identified a two‐gene family of proteins involved in lipid droplet biogenesis, which we name Fat storage‐Inducing Transmembrane protein (FITM1/FIT1 & FITM2/FIT2. FITM2 is ubiquitously expressed in tissues with high expression in white and brown adipose tissue. Overexpression of either member of the FITM family results in increased accumulation of cytosolic lipid droplets both in vitro and in vivo, not by enhancing triglyceride synthesis but by partitioning newly synthesized triglyceride into lipid droplets. To understand the role of FITM2 in lipid droplet biogenesis in vivo we generated adipose tissue‐specific knockouts (AF2KO) using the aP2‐cre to drive gene deletion of FIT2 in mature adipocytes. AF2KO mice exhibited protection from diet‐induced weight gain, which correlated with a 40% decreased in fat mass relative to wild‐type mice. This was due to an increased in basal and isoproterenol stimulated lipolysis in white fat pads isolated from AF2KO mice. AF2KO mice exhibited massive increased accumulation of adipose tissue macrophage, but this did not result in changes in glucose or insulin tolerance. Taken together our studies indicate that FIT2 plays an important role in triglyceride storage in mature adipocytes in vivo.