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Protein Family Identified As Key Mediator in Fat Storage

Conserved gene induces lipid droplet accumulation

FRIDAY, Jan. 4 (HealthDay News) -- A conserved gene family named fat-inducing transcript (FIT) is important for the formation of cytoplasmic triglyceride lipid droplets, according to a report published online Dec. 26 in the Proceedings of the National Academy of Sciences Early Edition.

Bert Kadereit, of the Albert Einstein College of Medicine, Bronx, N.Y., and colleagues searched for proteins that mediate lipid droplet biogenesis in the endoplasmic reticulum. RNA was purified from mouse livers to generate cDNA probes used to query a gene array, focusing on genes listed as ESTs or having unknown function. After identifying two unknown transcripts, identified as FIT1 and FIT2, Northern and Western blot analyses were performed, together with analyses to determine the subcellular localization of FITs and their role in lipid metabolism and triglyceride biogenesis. Finally, the findings were tested on lipid metabolism in zebrafish.

Several lines of evidence suggest the importance of FIT proteins in the accumulation of lipid droplets. They are evolutionarily conserved and exclusively located in the endoplasmic reticulum. When FITs are overexpressed in cultured cells of mouse liver in vivo, triglyceride-rich lipid droplets accumulate, but accumulation is reduced by the depletion of FIT2 in 3T3-L1 adipocytes or knockdown of FIT2 in zebrafish embryos.

"The identification of FIT proteins should facilitate the development of reagents to regulate FIT expression or activity to treat diseases associated with excessive lipid droplet accumulation, such as obesity, type 2 diabetes, and atherosclerosis," the authors conclude.

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