Once considered an inert storage organ, adipose tissue is now known to have numerous metabolic as well as endocrine functions. In contrast to the major lipid storage function of white adipose tissue (WAT), brown adipose tissue (BAT) generates heat through nonshivering thermogenesis, or generation of heat by uncoupling of the proton gradient of the electron transport chain from ATP synthesis.
Hypoxia-inducible gene 2 (Hig2) is a 63 amino acid protein that was previously identified as a protein that localizes to lipid droplets (LDs) in hepatocytes and promotes hepatic lipid deposition by inhibiting lipolysis.
In the present study, DiStefano and colleagues observed that Hig2 is highly expressed in the adipocyte fraction of adipose tissue samples. They demonstrate that Hig2 also localizes to LDs in adipocytes and its expression is increased with both adipogenic differentiation and fat deposition in vitro, suggesting that Hig2 may also play a role in adipose tissue in vivo. Mice harboring an adipocyte-specific deletion of Hig2 demonstrate reduced epididymal fat pad weight and improved glucose tolerance after high fat diet. These effects are abrogated by thermoneutral housing, suggesting that Hig2 may have an unexpected role in BAT in addition to WAT function. Taken together, these results suggest that adipocyte-specific Hig2 promotes adipocyte lipid deposition and glucose intolerance.Full Text