Synthetic phosphoinositolglycans regulate lipid metabolism between rat adipocytes via release of GPI-protein-harbouring adiposomes.
A novel molecular mechanism for the regulation of lipid metabolism by palmitate, H2O2 and the anti-diabetic sulfonylurea drug, glimepiride, in rat adipocytes was recently elucidated. It encompasses the translocation of the glycosylphosphatidylinositol-anchored (GPI-) and (c)AMP degrading enzymes Gce1 and CD73 from detergent-insoluble glycolipid-enriched microdomains of the plasma membrane (DIGs) to intracellular lipid droplets (LD), the incorporation of Gce1 and CD73 into vesicles (adiposomes) which are then released from donor adipocytes and finally the transfer of Gce1 and CD73 from the adiposomes to acceptor adipocytes, where they degrade (c)AMP at the LD surface. Here the stimulation of esterification and inhibition of lipolysis by synthetic phosphoinositolglycans (PIGs), such as PIG37, which represents the glycan component of the GPI anchor, are shown to be correlated to translocation from DIGs to LD and release into adiposomes of Gce1 and CD73. PIG37 actions were blocked upon disruption of DIGs, inactivation of PIG receptor and removal of adiposomes from the incubation medium as was true for those induced by palmitate, H2O2 or glimepiride. In contrast, only the latter actions were dependent on the GPI-specific phospholipase C (GPI-PLC), which may generate PIGs, or on exogenous PIG37 in case of inhibited GPI-PLC. At submaximal concentrations PIG37 and palmitate, H2O2 or glimepiride acted in synergistic fashion. These data suggest that PIGs provoke the transfer of GPI-proteins from DIGs via LD and adiposomes of donor adipocytes to acceptor adipocytes and thereby mediate the regulation of lipid metabolism by palmitate, H2O2 and glimepiride between adipocytes.
Sanofi-Aventis Deutschland GmbH, Research & Development, 65926 Frankfurt am Main, Germany. Guenter.Mueller@sanofiaventis.com
Günter
G
Müller
Andrea
A
Schulz
Elisabeth-Ann
EA
Dearey
Eva-Maria
EM
Wetekam
Susanne
S
Wied
Wendelin
W
Frick
D015720:5'-Nucleotidase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007295:Inositol Phosphates / Q000138:chemical synthesis* / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D011134:Polysaccharides; D011506:Proteins; C028039:inositol phosphate glycan; D015720:5'-Nucleotidase