What activates thermogenesis when lipid droplet lipolysis is absent in brown adipocytes?

Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD–LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.

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

Molecular and Cellular Biology ◽

10.1128/mcb.01269-09 ◽

2009 ◽

Vol 30 (5) ◽

pp. 1231-1242 ◽

Cited By ~ 31

Author(s):

Angela Hommel ◽

Deike Hesse ◽

Wolfgang Völker ◽

Alexander Jaschke ◽

Markus Moser ◽

...

Keyword(s):

Lipid Droplet ◽

Protein Trafficking ◽

Lipid Droplets ◽

Hormone Sensitive Lipase ◽

Droplet Growth ◽

Brown Adipocytes ◽

Brown Adipose ◽

Hormone Sensitive ◽

Intracellular Organelles ◽

Adp Ribosylation Factor

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.

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