Control of Lipolysis by Perilipins

The perilipins are a family of 5 proteins that are among the most abundant lipid droplet‐associated proteins in animal cells; most cells in the body express 2 – 4 perilipins. Perilipins form organizing scaffolds at the surfaces of lipid droplets to coordinate the activity of lipases and other factors. Different cells express different combinations of lipases; hence, lipolysis is controlled by a unique combination of perilipins and lipases in a cell‐specific manner. In adipocytes, perilipin 1 serves a critical function in the control of lipolysis catalyzed by hormone‐sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). Under basal (fed) conditions, perilipin 1 restricts the access of lipases to lipid droplets, thus promoting the storage of triacylglycerols. Following binding of catecholamines to cell surface receptors of adipocytes, phosphorylation of perilipin 1 by protein kinase A promotes lipolysis through multiple mechanisms including facilitating recruitment and binding of HSL to lipid droplets and release of CGI‐58, a co‐activator of ATGL, from the perilipin scaffold. Perilipin 5 is highly expressed in oxidative tissues including heart and skeletal muscle, where ATGL and HSL catalyze lipolysis. Perilipin 5 binds both CGI‐58 and ATGL at lipid droplet surfaces, and serves as a negative regulator of lipolysis under basal conditions. Supported by NIH R01 DK54797.