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Transfer of the glycosylphosphatidylinositol‐anchored 5′‐nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis
Author(s) -
Müller G,
Jung C,
Wied S,
BiemerDaub G,
Frick W
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00724.x
Subject(s) - glimepiride , chemistry , downregulation and upregulation , lipid droplet , microbiology and biotechnology , biochemistry , perilipin , adipocyte , biology , endocrinology , adipose tissue , insulin , metformin , gene
Background and purpose: In addition to predominant localization at detergent‐insoluble, glycolipid‐enriched plasma membrane microdomains (DIGs), glycosylphosphatidylinositol (GPI)‐anchored proteins (GPI‐proteins) have been found associated with lipid droplets (LDs) and adiposomes. Adiposomes are vesicles that are released from adipocytes in response to anti‐lipolytic and lipogenic signals, such as H 2 O 2 , palmitate and the antidiabetic sulfonylurea drug, glimepiride, and harbour (c)AMP‐degrading GPI‐proteins, among them the 5‐nucleotidase CD73. Here the role of adiposomes in GPI‐protein‐mediated information transfer was studied. Experimental approach: Adiposomes were incubated with isolated rat adipocytes under various conditions. Trafficking of CD73 and lipid synthesis were analysed. Key results: Upon blockade of GPI‐protein trafficking, CD73 specifically associated with DIGs of small, and to a lower degree, large, adipocytes. On reversal of the blockade, CD73 appeared at cytosolic LD in time‐ adiposome concentration‐ and signal (H 2 O 2 > glimepiride > palmitate)‐dependent fashion. The salt‐ and carbonate‐resistant association of CD73 with structurally intact DIGs and LD was dependent on its intact GPI anchor. Upon incubation with small and to a lower degree, large adipocytes, adiposomes increased lipid synthesis in the absence or presence of H 2 O 2 , glimepiride and palmitate and improved the sensitivity toward these signals. Upregulation of lipid synthesis by adiposomes was dependent on the translocation of CD73 with intact GPI anchors from DIGs to LD. Conclusions: The signal‐induced transfer of GPI‐anchored CD73 from adiposomes via DIGs to LD of adipocytes mediates paracrine upregulation of lipid synthesis within the adipose tissue.