title: Fat storage-inducing transmembrane protein 2 is required for normal fat storage in adipose tissue.
abstract: Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo.
authors: From the Signature Research Program in Cardiovascular and Metabolic Disorders and.
authors: Diego A
authors: DA
authors: Miranda
authors: Ji-Hyun
authors: JH
authors: Kim
authors: Long N
authors: LN
authors: Nguyen
authors: Wang
authors: W
authors: Cheng
authors: Bryan C
authors: BC
authors: Tan
authors: Vera J
authors: VJ
authors: Goh
authors: Jolene S Y
authors: JS
authors: Tan
authors: Jadegoud
authors: J
authors: Yaligar
authors: Bhanu Prakash
authors: BP
authors: Kn
authors: S Sendhil
authors: SS
authors: Velan
authors: Hongyan
authors: H
authors: Wang
authors: David L
authors: DL
authors: Silver
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C526205:FIT2 protein, mouse; D008565:Membrane Proteins; D014280:Triglycerides
keywords: Endoplasmic Reticulum (ER); Lipid Droplets; Lipodystrophy; Membrane Proteins; Obesity