| First Author | Glorian M | Year | 1998 |
| Journal | J Cell Biochem | Volume | 68 |
| Issue | 3 | Pages | 298-308 |
| PubMed ID | 9518257 | Mgi Jnum | J:47051 |
| Mgi Id | MGI:1202556 | Doi | 10.1002/(sici)1097-4644(19980301)68:3<298::aid-jcb2>3.0.co;2-p |
| Citation | Glorian M, et al. (1998) Glucocorticoids repress induction by thiazolidinediones, fibrates, and fatty acids of phosphoenolpyruvate carboxykinase gene expression in adipocytes. J Cell Biochem 68(3):298-308 |
| abstractText | Phosphoenolpyruvate carboxykinase (PEPCK) exerts a glyceroneogenic function in adipocytes in which transcription of its gene is increased by unsaturated fatty acids and fibrates. We used cultured rat adipose tissue fragments and 3T3-F442A adipocytes to show that the antidiabetic thiazolidinedione BRL 49653, a ligand and an activator of the gamma isoform of peroxisome proliferator activated receptors (PPARgamma), is a potent inducer of PEPCK mRNA. In 3T3-F442A adipocytes, the effect of BRL 49653 is rapid and concentration dependent, with a maximum reached at 1 microM and a half-maximum at 10-100 nM. PEPCK mRNA is similarly induced by the natural ligand of PPARgamma, the 15-deoxy-delta(12-14) prostaglandin J2. These observations strongly suggest that PPARgamma is a primary regulator of PEPCK gene expression in adipocytes. Dexamethasone at 10 nM repress induction of PEPCK mRNA by 1 microM BRL 49653, 0.32 mM oleate, or 1 mM clofibrate, in a cycloheximide- independent manner. The antiglucocorticoid RU 38486 prevents dexamethasone action, demonstrating involvement of the glucocorticoid receptor. Stable transfectants of 3T3-F442A adipocytes bearing -2100 to +69 base pairs of the PEPCK gene promoter fused to the chloramphenicol acetyltransferase (CAT) gene respond to 1 microM BRL 49653 or 1 mM clofibrate by a large increase in CAT activity, which is prevented by the simultaneous addition of 10 nM dexamethasone. Hence, in adipocytes, glucocorticoids act directly through the 5'-flanking region of the PEPCK gene to repress, in a dominant fashion, the stimulation of PEPCK gene transcription by thiazolidinediones and fibrates. |
