title: FAM3A is a target gene of peroxisome proliferator-activated receptor gamma.
abstract: 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).
  
  
  RESULTS
  The transcriptional activity of human and mouse FAM3A gene promoters was determined by luciferase reporter assay system. PPARγ agonist rosiglitazone induced FAM3A expression in primary cultured mouse hepatocytes and human HepG2 cells. PPARγ antagonism blocked rosiglitazone-induced FAM3A expression, whereas PPARγ overexpression stimulated FAM3A expression in HepG2 cells. In contrast, PPARα agonist fenofibrate or PPARβ agonist GW0742 failed to affect FAM3A expression in HepG2 cells. The transcriptional activities of human and mouse FAM3A promoters were markedly stimulated by PPARγ activation, but not by PPARα and PPARβ activation. Chromatin immunoprecipitation (ChIP) assay revealed a direct binding of PPARγ 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 PPARγ'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 PPARγ activation was correlated with increased level of phosphorylated Akt (pAkt) in liver cells.
  
  
  CONCLUSIONS
  FAM3A as a novel target gene of PPARγ. Upregulation of FAM3A by PPARγ activation is correlated with increased pAkt level in liver cells.
  
  
  CONCLUSIONS
  Upregulation of FAM3A might contribute to PPARγ's metabolic effects in the liver.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shi
authors.initials: S
authors.lastname: Jia
authors.forename: Chunjiong
authors.initials: C
authors.lastname: Wang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Yujing
authors.initials: Y
authors.lastname: Chi
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Guoheng
authors.initials: G
authors.lastname: Xu
authors.forename: Youfei
authors.initials: Y
authors.lastname: Guan
authors.forename: Jichun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000502:physiology*; D010168:Palmitates / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D016207:Cytokines; C582880:FAM3A protein, human; D047495:PPAR gamma; D010168:Palmitates; D045162:Thiazolidinediones; D000077154:Rosiglitazone