Thiazolidinediones downregulate stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes.
Thiazolidinediones (TZDs) are known to have potent increases of insulin sensitivity. Because peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a receptor for TZDs, is mainly expressed in adipocytes, we tried to search the TZD-targeted genes in mouse 3T3-L1 adipocytes. By the mRNA differential display method, one band repressed by troglitazone was obtained, which corresponded to the partial sequences of the stearoyl-CoA desaturase 1 (SCD1) gene. Troglitazone dramatically decreased SCD1 mRNA levels in 3T3-L1 adipocytes in a dose-dependent manner. Pioglitazone also repressed the SCD1 mRNA expression, whereas WY-14,643 had no apparent effect. Both troglitazone and pioglitazone raised the composition (weight percentage) of myristic acid (C14:0), palmitic acid (C16:0), and stearic acid (C18:0), but lowered the composition of the delta9-cis desaturated fatty acids such as myristoleic acid (C14:1, delta9), palmitoleic acid (C16:1, delta9), oleic acid (C18:1, delta9), and linoleic acid (C18:2, delta9,12). These results indicate that TZDs repress SCD1 activity in 3T3-L1 adipocytes via downregulating SCD1 enzyme gene expression.
Kurebayashi
S
S
Department of Medicine III, Osaka University Medical School, Suita City, Japan.
Hirose
T
T
Miyashita
Y
Y
Kasayama
S
S
Kishimoto
T
T
D016475:3T3 Cells; D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D015152:Blotting, Northern; D002839:Chromans / Q000494:pharmacology; D015342:DNA Probes; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D015342:DNA Probes; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D013230:Stearoyl-CoA Desaturase; D000077288:Troglitazone; D000077205:Pioglitazone