JAZF1 可以调节脂肪代谢基因的表达，抑制脂肪细胞中的脂质积累。
JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes.
机构信息
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China; Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China.
出版信息
Biochem Biophys Res Commun. 2014 Mar 14;445(3):673-80. doi: 10.1016/j.bbrc.2014.02.088. Epub 2014 Feb 26.
JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.
JAZF1 是一个新鉴定的具有未知功能的基因。最近的全基因组关联研究表明，JAZF1 与 2 型糖尿病有关，在肝脏和脂肪组织中高度表达。研究表明，JAZF1 是核孤儿受体 TAK1 的共阻遏物，而大多数核孤儿受体家族成员参与脂质代谢的调节。因此，JAZF1 可能与糖脂代谢密切相关。在这项研究中，JAZF1 在 3T3-L1 前脂肪细胞的诱导分化过程中显著上调。JAZF1 的过表达抑制了分化成熟的 3T3-L1 脂肪细胞中的脂质积累，并显著抑制了脂质合成中重要的 SREBPl、ACC 和 FAS 的表达，同时上调了脂肪分解中关键酶激素敏感性脂肪酶的表达。此外，SREBPl 对 JAZF1 的表达具有抑制作用。SREBP1 逆转了 JAZF1 对脂质积累的抑制作用。SREBP1 和 JAZF1 在脂肪细胞中相互调节。因此，JAZF1 可以调节与脂质代谢相关的特定基因的表达，并抑制脂肪细胞中的脂质积累。这一结果表明，JAZF1 可能是肥胖和脂质代谢紊乱等疾病治疗的潜在靶点。
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