Lipid storage in large and small rat adipocytes by vesicle-associated glycosylphosphatidylinositol-anchored proteins.
Adipose tissue mass in mammals expands by increasing the average cell volume and/or total number of the adipocytes. Upregulated lipid storage in fully differentiated adipocytes resulting in their enlargement is well documented and thought to be a critical mechanism for the expansion of adipose tissue depots during the growth of both lean and obese animals and human beings. A novel molecular mechanism for the regulation of lipid storage and cell size in rat adipocytes was recently elucidated for the physiological stimuli, palmitate and H(2)O(2), and the antidiabetic sulfonylurea drug, glimepiride. It encompasses (1) the release of small vesicles, so-called adiposomes, harboring the glycosylphosphatidylinositol -anchored (c)AMP-degrading phosphodiesterase Gce1 and 5'-nucleotidase CD73 from donor adipocytes, (2) the transfer of the adiposomes and their interaction with detergent-insoluble glycolipid-enriched microdomains of the plasma membrane of acceptor adipocytes, (3) the translocation of Gce1 and CD73 from the adiposomes to the intracellular lipid droplets of the acceptor adipocytes, and (4) the degradation of (c)AMP at the lipid droplet surface zone by Gce1 and CD73 in the acceptor adipocytes, leading to the upregulation of the esterification of fatty acids into triacylglycerol s and the downregulation of their release from triacylglycerols. This mechanism may provide novel strategies for the therapy of metabolic diseases, such as type 2 diabetes and obesity.
Müller
Günter
G
Sanofi-Aventis Deutschland GmbH, Research & Development, 65926 Frankfurt, Germany. Guenter.Mueller@sanofi-aventis.com
Wied
Susanne
S
Dearey
Elisabeth-Ann
EA
Wetekam
Eva-Maria
EM
Biemer-Daub
Gabriele
G
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D048429:Cell Size; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats
D017261:Glycosylphosphatidylinositols; D050683:R-SNARE Proteins