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 (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.
Hommel
Angela
A
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
Hesse
Deike
D
Völker
Wolfgang
W
Jaschke
Alexander
A
Moser
Markus
M
Engel
Thomas
T
Blüher
Matthias
M
Zahn
Claudia
C
Chadt
Alexandra
A
Ruschke
Karen
K
Vogel
Heike
H
Kluge
Reinhart
R
Robenek
Horst
H
Joost
Hans-Georg
HG
Schürmann
Annette
A
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
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