| First Author | Zhou Y | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1830 |
| Issue | 8 | Pages | 4160-70 |
| PubMed ID | 23562554 | Mgi Jnum | J:202406 |
| Mgi Id | MGI:5518991 | Doi | 10.1016/j.bbagen.2013.03.029 |
| Citation | Zhou Y, et al. (2013) FAM3A is a target gene of peroxisome proliferator-activated receptor gamma. Biochim Biophys Acta 1830(8):4160-70 |
| abstractText | BACKGROUND: To date, the biological function of FAM3A, the first member of FAM3 gene family, remains unknown. We aimed to investigate whether the expression of FAM3A in liver cells is regulated by peroxisome proliferator-activated receptors (PPARs). METHODS AND RESULTS: The transcriptional activity of human and mouse FAM3A gene promoters was determined by luciferase reporter assay system. PPARgamma agonist rosiglitazone induced FAM3A expression in primary cultured mouse hepatocytes and human HepG2 cells. PPARgamma antagonism blocked rosiglitazone-induced FAM3A expression, whereas PPARgamma overexpression stimulated FAM3A expression in HepG2 cells. In contrast, PPARalpha agonist fenofibrate or PPARbeta agonist GW0742 failed to affect FAM3A expression in HepG2 cells. The transcriptional activities of human and mouse FAM3A promoters were markedly stimulated by PPARgamma activation, but not by PPARalpha and PPARbeta activation. Chromatin immunoprecipitation (ChIP) assay revealed a direct binding of PPARgamma to the putative peroxisome proliferator response element (PPRE) located at -1258/-1246 in the human FAM3A promoter. Site-directed mutagenesis of this PPRE-like motif abolished PPARgamma's stimulatory effect on the transcriptional activity of human FAM3A promoter. In vivo, oral rosiglitazone treatment upregulated FAM3A expression in the livers of C57BL/6 mice and db/db mice. Moreover, upregulation of FAM3A by PPARgamma activation was correlated with increased level of phosphorylated Akt (pAkt) in liver cells. CONCLUSIONS: FAM3A as a novel target gene of PPARgamma. Upregulation of FAM3A by PPARgamma activation is correlated with increased pAkt level in liver cells. GENERAL SIGNIFICANCE: Upregulation of FAM3A might contribute to PPARgamma's metabolic effects in the liver. |
