title: JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Guang-feng
authors.initials: GF
authors.lastname: Ming
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China.
authors.forename: Wei-jing
authors.initials: WJ
authors.lastname: Gong
authors.affiliation: Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Hui-xia
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China.
authors.forename: Hong-hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China. Electronic address: liuzhaoqian63@126.com.
authors.forename: Zhao-qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C558308:JAZF1 protein, mouse; D008055:Lipids; D009687:Nuclear Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D005947:Glucose
keywords: 3T3-L1; Adipocytes; JAZF1; Lipid accumulation; SREBP1; TAK1