Control of lipid storage and cell size between adipocytes by vesicle-associated glycosylphosphatidylinositol-anchored proteins.
Adipose tissue mass in mammals is expanding by increasing the average cell volume as well as the total number of the adipocytes. Up-regulation of 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 has recently been elucidated for the physiological stimuli, palmitate and hydrogen peroxide, the anti-diabetic sulfonylurea drug, glimepiride, and insulin-mimetic phosphoinositolglycans. It encompasses (i) the release of small vesicles, so-called adiposomes, harbouring the glycosylphosphatidylinositol-anchored (c)AMP-degrading phosphodiesterase Gce1 and 5'-nuceotidase CD73 from large donor adipocytes, (ii) the transfer of the adiposomes and their interaction with detergent-insoluble glycolipid-enriched microdomains of the plasma membrane of small acceptor adipocytes, (iii) the translocation of Gce1 and CD73 from the adiposomes to the intracellular lipid droplets of the acceptor adipocytes and (iv) the degradation of (c)AMP at the lipid droplet surface zone by Gce1 and CD73 in the acceptor adipocytes. In concert, this sequence of events leads to up-regulation of esterification of fatty acids into triacylglycerol and down-regulation of their release from triacylglycerol. This apparent mechanism for shifting the triacylglycerol burden from large to small adipocytes may provide novel strategies for the therapy of metabolic diseases, such as type 2 diabetes and obesity.
Müller
Günter
G
Ludwig-Maximilians-University Munich, Biocenter, Department Biology I, Genetics Martinsried, Germany. Guenter.Mueller@sanofi-aventis.com
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D001692:Biological Transport; D016764:Cell Polarity; D048429:Cell Size; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D058635:Lipid-Linked Proteins / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D021962:Membrane Microdomains / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D051381:Rats; D022161:Transport Vesicles / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D007004:Hypoglycemic Agents; D007328:Insulin; D058635:Lipid-Linked Proteins; D014280:Triglycerides; D006867:Hydrolases