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The inhibitory guanine nucleotide‐binding protein G i2 α induces and potentiates adipocyte differentiation
Author(s) -
Høvik Kjerstin E.,
Wu Pengfei,
Gordeladze Jan O.
Publication year - 1999
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-999-0373-9
Subject(s) - cellular differentiation , phosphatidylinositol , phosphatidylethanolamine , adipocyte , lipid droplet , biochemistry , microbiology and biotechnology , chemistry , phospholipid , biology , phosphatidylcholine , kinase , gene , adipose tissue , membrane
The present study further elucidates the involvement of the α‐subunit of the GTP‐binding protein G i2 in the differentiation of murine 313‐L1 cells. Control and vector‐transfected cells attained a fully differentiated adipocyte phenotype showing ample lipid droplets. Cells expressing wild type (WT)‐G i2 α or the constitutively active R179E‐G i2 α, however, became enlarged, less confluent, and produced large amounts of lipids. Differentiation consistently increased the triglyceride (TAG) content in control cells. In both WT‐G i2 α and R179E‐G i2 α clones, a marked increase in TAG could be detected even prior to insulin/dexamethasone/isobutyl methylxanthine exposure. The activity of palmitoyl‐CoA synthetase (PCS) and glycerophosphate acyltransferase (GPAT) also increased upon differentiation. WT‐G i2 α and R179E‐G i2 α overexpression also enhanced PCS and GPAT activities even before differentiation medium was added. The total amount of phospholipids (PL) generally increased upon differentiation; however, pre‐ and postdifferentiation values were insignificantly different in cells expressing WT‐G i2 α and R179E‐G i2 α. Differentiation altered the PL profile with a relative shift from phosphatidylcholine and phosphatidylethanolamine to phosphatidylinositol (PI) in differentiated cells. Finally, differentiation yielded a general increase in the activity of basal PI‐phospholipase‐C activity. Again, cells expressing WT‐G i2 α and R179E‐G i2 α demonstrated elevated enzyme activity and enhanced second messenger accumulation subsequent to differentiation. In summary, cells with the R179E‐mutants of G i2 α exhibited stimulated lipid turnover and accumulation in both undifferentiated and differentiated cells.