The role of JAZF1 on lipid metabolism and related genes in vitro.

JAZF1 is a novel gene 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. In the present study, we have shown the expression of JAZF1 in various mouse tissues. To elucidate its role in metabolism, we investigated the influence of an overexpression of JAZF1 on 3T3-L1 adipose cells and hepatoma carcinoma Hepa1-6 cells that represent target tissues for diabetes and insulin resistance. In both cells, JAZF1 overexpression led to a substantial reduction in the expression of acetyl-coenzyme A carboxylase, fatty acid synthetase, and sterol regulatory element-binding protein 1 messenger RNA (mRNA). The level of hormone-sensitive lipase mRNA significantly increased. The expression of JAZF1 in 3T3-L1 adipocyte exhibited suppressive effects on lipid accumulation and decreased droplet size. In addition, the transcription for glucose transport 1 was significantly higher than the control in the Hepa1-6 cell line; but it was not significantly different in 3T3-L1. These results showed that JAZF1 in adipocytes and liver cells reduces lipid synthesis and increases lipolysis mainly by down-regulating the levels of sterol regulatory element-binding protein 1, acetyl-coenzyme A carboxylase, and fatty acid synthetase mRNA expression and by increasing hormone-sensitive lipase mRNA expression. Because it had an effect on the decrease of the maturation of lipid droplets and fat storage, we speculate that JAZF1 might represent a potential target against diabetes and obesity.