Zinc finger protein ZNF638 regulates triglyceride metabolism via ANGPTL8 in an estrogen dependent manner
文献类型：期刊论文
| 作者 | Meng, Meiyao1,2; Cao, Yuxiang1; Qiu, Jin1; Shan, Guangyu1; Wang, Yingwen1; Zheng, Ying1; Guo, Mingwei1; Yu, Jian1,3; Ma, Yuandi4; Xie, Cen4,5
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| 刊名 | METABOLISM-CLINICAL AND EXPERIMENTAL
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| 出版日期 | 2024-03-01 |
| 卷号 | 152页码:12 |
| 关键词 | Triglyceride metabolism ZNF638 Adipose tissue Angptl8 Lipoprotein lipase |
| ISSN号 | 0026-0495 |
| DOI | 10.1016/j.metabol.2024.155784 |
| 通讯作者 | Ma, Xinran(xrma@bio.ecnu.edu.cn) |
| 英文摘要 | Background and aim: Triglyceride (TG) levels are closely related to obesity, fatty liver and cardiovascular diseases, while the regulatory factors and mechanism for triglyceride homeostasis are still largely unknown. Zinc Finger Protein 638 (ZNF638) is a newly discovered member of zinc finger protein family for adipocyte function in vitro. The aim of the present work was to investigate the role of ZNF638 in regulating triglyceride metabolism in mice. Methods: We generated ZNF638 adipose tissue specific knockout mice (ZNF638 FKO) by cross-breeding ZNF638 flox to Adiponectin-Cre mice and achieved adipose tissue ZNF638 overexpression via adenoviral mediated ZNF638 delivery in inguinal adipose tissue (iWAT) to examined the role and mechanisms of ZNF638 in fat biology and whole-body TG homeostasis. Results: Although ZNF638 FKO mice showed similar body weights, body composition, glucose metabolism and serum parameters compared to wild -type mice under chow diet, serum TG levels in ZNF638 FKO mice were increased dramatically after refeeding compared to wild -type mice, accompanied with decreased endothelial lipoprotein lipase (LPL) activity and increased lipid absorption of the small intestine. Conversely, ZNF638 overexpression in iWAT reduced serum TG levels while enhanced LPL activity after refeeding in female C57BL/ 6J mice and obese ob/ob mice. Specifically, only female mice exhibited altered TG metabolism upon ZNF638 expression changes in fat. Mechanistically, RNA-sequencing analysis revealed that the TG regulator angiopoietinlike protein 8 (Angptl8) was highly expressed in iWAT of female ZNF638 FKO mice. Neutralizing circulating ANGPTL8 in female ZNF638 FKO mice abolished refeeding-induced TG elevation. Furthermore, we demonstrated that ZNF638 functions as a transcriptional repressor by recruiting HDAC1 for histone deacetylation and broad lipid metabolic gene suppression, including Angptl8 transcription inhibition. Moreover, we showed that the sexual dimorphism is possibly due to estrogen dependent regulation on ZNF638-ANGPTL8 axis. Conclusion: We revealed a role of ZNF638 in the regulation of triglyceride metabolism by affecting Angptl8 transcriptional level in adipose tissue with sexual dimorphism. |
| WOS关键词 | GENE ; MICE |
| 资助项目 | National Natural Science Foundation of China[31770840] ; National Natural Science Foundation of China[32325024] ; National Natural Science Foundation of China[32222024] ; National Natural Science Foundation of China[32271224] ; National Natural Science Foundation of China[32071148] ; National Key Research and Development Program of China[2019YFA0904500] ; Natural Science Foundation of Chongqing[CSTB2022NSCQJQX0033] ; Natural Science Foundation of Shanghai[22ZR1421200] ; Science and Technology Commission of Shanghai, Science and Technology Innovation Action Plan[21140904300] ; ECNU public platform for Innovation[011] ; Fundamental Research Funds for the Central Universities ; Instruments sharing platform of School of Life Sciences |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:001163032000001 |
| 出版者 | W B SAUNDERS CO-ELSEVIER INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309560]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ma, Xinran |
| 作者单位 | 1.East China Normal Univ, Inst Biomed Sci, Sch Life Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China 2.Chongqing Inst East China Normal Univ, Chongqing Key Lab Precis Opt, Chongqing 401120, Peoples R China 3.Southern Med Univ, Dept Endocrinol & Metab, Fengxian Cent Hosp, Shanghai 201499, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Shanghai Jiao Tong Univ, Shanghai Diabet Inst, Shanghai Clin Ctr Diabet, Shanghai Key Lab Diabet Mellitus,Affiliated People, Shanghai 200233, Peoples R China 6.NYU, Grossman Sch Med, Div Endocrinol Diabet & Metab, Dept Med, New York, NY USA |
| 推荐引用方式 GB/T 7714 | Meng, Meiyao,Cao, Yuxiang,Qiu, Jin,et al. Zinc finger protein ZNF638 regulates triglyceride metabolism via ANGPTL8 in an estrogen dependent manner[J]. METABOLISM-CLINICAL AND EXPERIMENTAL,2024,152:12. |
| APA | Meng, Meiyao.,Cao, Yuxiang.,Qiu, Jin.,Shan, Guangyu.,Wang, Yingwen.,...&Ma, Xinran.(2024).Zinc finger protein ZNF638 regulates triglyceride metabolism via ANGPTL8 in an estrogen dependent manner.METABOLISM-CLINICAL AND EXPERIMENTAL,152,12. |
| MLA | Meng, Meiyao,et al."Zinc finger protein ZNF638 regulates triglyceride metabolism via ANGPTL8 in an estrogen dependent manner".METABOLISM-CLINICAL AND EXPERIMENTAL 152(2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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