Inhibition of lipolysis by adiposomes containing glycosylphosphatidylinositol-anchored Gce1 protein in rat adipocytes.
Small membrane vesicles released from large adipocytes and harbouring the glycosylphosphatidylinositol-anchored (GPI-) AMP-degrading protein CD73 have previously been demonstrated to stimulate the signal-induced esterification of free fatty acids into neutral lipids suggesting a role of these so-called adiposomes (ADIP) in the paracrine regulation of lipid metabolism in the adipose tissue. Here the involvement of another constituent GPI-protein of ADIP, the cAMP-degrading protein Gce1 in the signal-induced inhibition of lipolysis was investigated in primary rat adipocytes. Incubation of small, and to a lower degree, large adipocytes with ADIP inhibited lipolysis and increased its sensitivity toward inhibition by H(2)O(2), the anti-diabetic drug glimepiride and palmitate. This was accompanied by the transfer of Gce1 from the ADIP to detergent-insoluble glycolipid-enriched plasma membrane microdomains (DIGs) and its subsequent translocation to cytoplasmic lipid droplets (LD) of the acceptor adipocytes. The translocation from DIGs to LD rather than the transfer from ADIP to DIGs of Gce1 was stimulated by H(2)O(2) > glimepiride > palmitate. Both transfer and translocation led to salt- and carbonate-resistant association of Gce1 with DIGs and LD, respectively, and relied on the structural integrity of the DIGs and GPI anchor of Gce1. In conclusion, the trafficking of GPI-proteins from ADIP of donor adipocytes via DIGs to LD of acceptor adipocytes mediates paracrine regulation of lipolysis within adipose tissue.
Müller
Günter
G
Sanofi-Aventis Germany GmbH, Germany. Guenter.Mueller@sanofi-aventis.com
Wied
Susanne
S
Jung
Christian
C
Frick
Wendelin
W
Biemer-Daub
Gabriele
G
D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022161:Transport Vesicles / Q000378:metabolism*
D017261:Glycosylphosphatidylinositols