Differential regulation of the stearoyl-CoA desaturase genes by thiazolidinediones in 3T3-L1 adipocytes.
Two stearoyl-CoA desaturase (SCD) isoforms can be expressed during the differentiation of 3T3-L1 preadipocytes into adipocytes. Here we report on the effects of the peroxisome proliferator-activated receptor gamma ligand troglitazone (TRO) on scd1 and scd2 mRNA levels as determined by Northern blotting, on SCD protein expression as determined by Western blotting, and on total lipid composition as determined by GC during differentiation. In preadipocytes, scd1 mRNA and SCD protein were not detected, whereas scd2 mRNA was detected. These cells have high levels of palmitate (16:0), stearate (18:0), and monounsaturated oleate (Delta(9)-18:1) and low levels of monounsaturated palmitoleate (Delta(9)-16:1). In MDI (methylisobutylxanthine, dexamethasone, and insulin)-treated cells, scd1 mRNA and SCD protein were increased approximately 100-fold relative to preadipocyte levels, the scd2 mRNA level was increased 2-fold, Delta(9)-16:1 was increased approximately 20-fold, and 18:0 was decreased approximately 3-fold. In TRO-treated cells, the scd1 mRNA level was lower than that observed in preadipocytes, while the scd2 mRNA level was similar. TRO also decreased scd1 mRNA in primary adipocytes. The TRO-treated cells contained a Delta(9)-18:1 level typical of MDI-treated cells whereas, conversely, these cells also contained a low Delta(9)-16:1 level typical of preadipocytes. The implications of these correlations for the regulatory and enzymatic mechanism(s) used to establish and maintain lipid composition are discussed.
Kim
Y C
YC
Departments of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI 53706, USA.
Gomez
F E
FE
Fox
B G
BG
Ntambi
J M
JM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells / Q000201:enzymology*; D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D008055:Lipids / Q000032:analysis; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism; D000077288:Troglitazone
D002839:Chromans; D005938:Glucocorticoids; D007328:Insulin; D007527:Isoenzymes; D008055:Lipids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D003907:Dexamethasone; D013230:Stearoyl-CoA Desaturase; D000077288:Troglitazone; D015056:1-Methyl-3-isobutylxanthine