title: The ARF-like GTPase ARFRP1 is essential for lipid droplet growth and is involved in the regulation of lipolysis.
abstract: 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 (synaptosomal-associated 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.
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Hommel
authors.forename: Deike
authors.initials: D
authors.lastname: Hesse
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Völker
authors.forename: Alexander
authors.initials: A
authors.lastname: Jaschke
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Thomas
authors.initials: T
authors.lastname: Engel
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Claudia
authors.initials: C
authors.lastname: Zahn
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chadt
authors.forename: Karen
authors.initials: K
authors.lastname: Ruschke
authors.forename: Heike
authors.initials: H
authors.lastname: Vogel
authors.forename: Reinhart
authors.initials: R
authors.lastname: Kluge
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
mesh_terms: D041721:3T3-L1 Cells; D020727:ADP-Ribosylation Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052437:Adipocytes, Brown / Q000378:metabolism / Q000648:ultrastructure; D052242:Adiponectin / Q000097:blood; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008060:Lipodystrophy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008066:Lipolysis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D010641:Phenotype; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D002787:Sterol Esterase / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D017931:DNA Primers; D020738:Leptin; D034741:RNA, Small Interfering; D002787:Sterol Esterase; D020727:ADP-Ribosylation Factors; C531986:Arfrp1 protein, mouse