JAZF1 (Juxtaposed with Another Zinc Finger gene 1) transcription factor are Zn-finger proteins that bind to the nuclear orphan receptor TAK/TR4 (Nakajima et al., 2004). The nuclear orphan receptor TAK1/TR4 functions as a positive as well as a negative regulator of transcription. It was recently reported that congenital cardiovascular malformations are significantly more frequent in Neurofibromatosis 1 (NF1) patients with microdeletion syndrome than in those with classical NF1. JAZF1 was expressed in adult heart of patients with microdeletion syndrome. JAZF1 is highly conserved among various species include zebrafish. We hypothesized that the expression of zebrafish Jazf1 may lead to severe forms of congenital heart disease that allow the survival of newborns and adults. In this study, we created Jazf1 transgenic zebrafish which over-express zebrafish Jazf1 cDNA under control of the CMV promoter. Our results suggested that Jazf1 expression may play an important role in zebrafish cardiac development.

JAZF1 is a 27 kDa nuclear protein containing two putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer according to genomewide association studies; however, little is known about the function of this gene in regulating metabolism. Recent evidence indicates that JAZF1 transcription factors bind to the nuclear orphan receptor TR4 and act as a strong repressor. This receptor regulates PEPCK, the key enzyme in gluconeogenesis, at the transcriptional level. Excess PEPCK expression in mice causes hyperglycemia, hyperinsulinemia, and increased glucose turnover. Therefore, we hypothesized that ectopic expression of Jazf1 may lead to abnormal expression of PEPCK that allow for the metabolic disorder. To elucidate its role in metabolism, we fed the mice with high- or normal- fat diet up to 18 weeks. In the liver tissue of mice, Jazf1 overexpression led to a substantial reduction in the expression of PEPCK. In Jazf1 overexpression mice, weight gain was found to be significantly decreased and increment of blood glucose level also decreased. Our data suggest that Jazf1 plays a critical role in the regulation of energy and lipid homeostasis, and promotes the development of metabolic disorder. Jazf1 may provide a new therapeutic target in the management of obesity, diabetes, and liver steatosis.