The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, Chongqing Medical University, 400016 Chongqing, China.
Metabolism. 2011 Apr;60(4):523-30. doi: 10.1016/j.metabol.2010.04.021. Epub 2010 Jun 30.
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.
JAZF1 是一个根据全基因组关联研究与糖尿病和前列腺癌相关的新基因；然而，关于该基因在调节代谢中的作用知之甚少。在本研究中，我们已经显示了 JAZF1 在各种小鼠组织中的表达。为了阐明其在代谢中的作用，我们研究了 JAZF1 过表达对代表糖尿病和胰岛素抵抗靶组织的 3T3-L1 脂肪细胞和肝癌 Hepa1-6 细胞的影响。在这两种细胞中，JAZF1 过表达导致乙酰辅酶 A 羧化酶、脂肪酸合成酶和固醇调节元件结合蛋白 1 信使 RNA（mRNA）的表达显著减少。激素敏感脂肪酶 mRNA 的水平显著增加。JAZF1 在 3T3-L1 脂肪细胞中的表达对脂质积累和减少液滴大小表现出抑制作用。此外，葡萄糖转运蛋白 1 的转录在 Hepa1-6 细胞系中明显高于对照，但在 3T3-L1 中差异不显著。这些结果表明，脂肪细胞和肝细胞中的 JAZF1 通过下调固醇调节元件结合蛋白 1、乙酰辅酶 A 羧化酶和脂肪酸合成酶 mRNA 表达水平，增加激素敏感脂肪酶 mRNA 表达水平，减少脂质合成和增加脂肪分解，主要是通过下调固醇调节元件结合蛋白 1、乙酰辅酶 A 羧化酶和脂肪酸合成酶 mRNA 表达水平，增加激素敏感脂肪酶 mRNA 表达水平。由于它对脂质滴成熟和脂肪储存的减少有影响，我们推测 JAZF1 可能是对抗糖尿病和肥胖的潜在靶点。
