J. Biol. Chem. 2014 289: 9560-. doi:10.1074/jbc.M114.547687
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 protein2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDsin cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we showthat adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots andmetabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs withoutchanges in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob backgroundaccelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissuedifferentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data supportthe conclusion that FIT2 plays an essential, physiological role in fat storage in vivo.
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Funding Info:
This work was supported in part by grants from the Singapore Ministry of Health’s National Medical Research Council CBRG/0012/2012 (to D. L. S.), the National Research Foundation Singapore under its NRF fellowship Award No. NRF2008NRF-RF001-117 (to H. W.), the Singapore Bioimaging Consortium, from the Agency for Science, Technology and Research (A*STAR) (to V. S. S.), and the National Science Scholarship award (to V. J. G.).