Abstract
Fat-specific protein 27 (Fsp27), a member of the CIDE family proteins, has been shown to be a lipid droplet-associated protein that promotes lipid storage in adipose tissue. Fsp27 knock-out mice have increased energy expenditure and are resistant to diet-induced obesity. Fsp27-induced lipid storage is mediated either by enhancing lipid droplet fusion or inhibiting lipolysis. However, the mechanism by which Fsp27 controls lipolysis remains unclear. Here, we observed that increased lipolysis in Fsp27 knockdown adipocytes was significantly abrogated when HSL was knocked down. In addition, we found that when co-expressed with Fsp27, HSL was excluded from lipid droplet surface. Furthermore, HSL exclusion was dependent on the C-terminal region of Fsp27. Our data indicate that Fsp27 regulates lipolysis by inhibiting the lipid droplet association of HSL, providing a novel mechanism for the regulation of lipid storage in adipose tissue and the development of obesity.
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