Abstract
Ghrelin secretion from the stomach acts on peripheral tissues to cause weight gain and fat accumulation in white adipose tissue (WAT). The role of endothelial growth hormone secretagogue-receptor (GHSR) in lipid accumulation was evaluated by restoring the expression of GHSR only in the endothelial cells of GHSR-deficient mice using the Cre-LoxP system (GHSR-EC). Radioisotope (RI) -labeled H-triolein was orally administered to evaluate lipid uptake in WAT. GHSR-deficient mice had reduced RI uptake in WAT compared to control mice, and GHSR-EC mice recovered the reduced RI uptake in GHSR-deficient mice. Furthermore, the body weight and WAT weight of GHSR-deficient mice after high-fat diet loading were significantly decreased compared with control mice, but increased in GHSR-EC mice. In vitro studies, ghrelin stimulation increased the uptake of free fatty acids by GHSR-mediated activation of the mTOR pathway and increased expression of PPARgamma. From these results, ghrelin takes up lipids via endothelial GHSR and contributes to fat accumulation in white adipose tissue.
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