The ARF-Like GTPase ARFRP1 Is Essential for Lipid Droplet Growth and Is Involved in the Regulation of Lipolysis

ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a GTPase regulating protein trafficking between intracellular organelles.Here we show that mice lacking Arfrp1 in adipocytes (Arfrp1 ad؊/؊ ) are lipodystrophic due to a defective lipid droplet formation in adipose cells.Ratios of mono-, di-, and triacylglycerol, as well as the fatty acid composition of triglycerides, were unaltered.Lipid droplets of brown adipocytes of Arfrp1 ad؊/؊ mice were considerably smaller and exhibited ultrastructural alterations, such as a disturbed interaction of small lipid-loaded particles with the larger droplets, suggesting that ARFRP1 mediates the transfer of newly formed small lipid particles to the large storage droplets.SNAP23 (synaptosomalassociated protein of 23 kDa) associated with small lipid droplets of control adipocytes but was located predominantly in the cytosol of Arfrp1 ad؊/؊ adipocytes, suggesting that lipid droplet growth is defective in Arfrp1 ad؊/؊ mice.In addition, levels of phosphorylated hormone-sensitive lipase (HSL) were elevated, and association of adipocyte triglyceride lipase (ATGL) with lipid droplets was enhanced in brown adipose tissue from Arfrp1 ad؊/؊ mice.Accordingly, basal lipolysis was increased after knockdown of Arfrp1 in 3T3-L1 adipocytes.The data indicate that disruption of ARFRP1 prevents the normal enlargement of lipid droplets and produces an activation of lipolysis.