Hepatic glucuronyl C5-epimerase combats obesity by stabilising GDF15
文献类型：期刊论文
| 作者 | He, Fei1,2,4,5; Jiang, Haowen1,2,5; Peng, Chang1,2,5; Wang, Tingting1,2,4,5; Xiao, Rongrong1,2,4,5; Chen, Meilin1,2,4,5; Song, Nixue1,2,5; Du, Zhenyun1,2,4,5; Wang, Hanlin1,2,5; Ding, Xiaoyu1,2,5 |
| 刊名 | JOURNAL OF HEPATOLOGY
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| 出版日期 | 2023-09-01 |
| 卷号 | 79期号:3页码:14 |
| ISSN号 | 0168-8278 |
| 关键词 | Glucuronyl C5-epimerase Growth differentiation factor-15 Obesity Energy expenditure Ubiquitination |
| DOI | 10.1016/j.jhep.2023.05.011 |
| 通讯作者 | Hua, Rong(dingkan@simm.ac.cn) ; Li, Jia(jli@simm.ac.cn) ; Ding, Kan(blossom875@sina.com) |
| 英文摘要 | Background & Aims: Disturbed hepatic metabolism frequently results in excessive lipid accumulation in the adipose tissue. However, the specific role of the liver-adipose axis in maintaining lipid homeostasis, as well as the underlying mechanism, has not yet been fully elucidated. In this study, we investigated the role of hepatic glucuronyl C5-epimerase (Glce) in the progression of obesity. Methods: We determined the association between the expression of hepatic Glce and body mass index (BMI) in obese patients. Obesity models were established in hepatic Glce-knockout and wild-type mice fed a high-fat diet (HFD) to understand the effect of Glce on obesity development. The role of Glce in the progression of disrupted hepatokine secretion was examined via secretome analysis.Results: Hepatic Glce expression was inversely correlated with BMI in obese patients. Moreover, Glce level was found to be decreased in the liver of a HFD murine model. Hepatic Glce deficiency led to impaired thermogenesis in adipose tissue and exacerbated HFD-induced obesity. Interestingly, decreased level of growth differentiation factor 15 (GDF15) was observed in the culture medium of Glce-knockout mouse hepatocytes. Treatment with recombinant GDF15 obstructed obesity progression derived from the absence of hepatic Glce, similar to the effect of Glce or its inactive mutant overexpressed both in vitro and in vivo. Furthermore, liver Glce deficiency led to diminished production and increased degradation of mature GDF15, resulting in reduced hepatic GDF15 secretion.Conclusions: Hepatic Glce deficiency facilitated obesity development, and decreased Glce expression further reduced hepatic secretion of GDF15, thereby perturbing lipid homeostasis in vivo. Therefore, the novel Glce-GDF15 axis plays an important role in maintaining energy balance and may act as a potential target for combating obesity.& COPY; 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
| WOS关键词 | MACROPHAGE INHIBITORY CYTOKINE ; INSULIN-RESISTANCE ; ACID ; MEMBER ; LIVER ; MIC-1 |
| 资助项目 | National Natural Science Foundation of China, China[31670814] ; National Natural Science Foundation of China, China[32000525] ; National Natural Science Foundation of China, China[82130099] ; Shanghai Municipal Science and Technology Major Project New Drug Creation and Manufacturing Program, China[2019ZX09735001] ; Lingang Laboratory, China[LG202103-03-01] ; China Postdoctoral Science Foundation, China[2021M703347] |
| WOS研究方向 | Gastroenterology & Hepatology |
| 语种 | 英语 |
| 出版者 | ELSEVIER |
| WOS记录号 | WOS:001066135000001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306152]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Hua, Rong; Li, Jia; Ding, Kan |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 3.Fudan Univ, Huashan Hosp, Ctr Obes & Metab Surg, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Drug Res Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou, Peoples R China 7.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Drug Res Ctr, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Fei,Jiang, Haowen,Peng, Chang,et al. Hepatic glucuronyl C5-epimerase combats obesity by stabilising GDF15[J]. JOURNAL OF HEPATOLOGY,2023,79(3):14. |
| APA | He, Fei.,Jiang, Haowen.,Peng, Chang.,Wang, Tingting.,Xiao, Rongrong.,...&Ding, Kan.(2023).Hepatic glucuronyl C5-epimerase combats obesity by stabilising GDF15.JOURNAL OF HEPATOLOGY,79(3),14. |
| MLA | He, Fei,et al."Hepatic glucuronyl C5-epimerase combats obesity by stabilising GDF15".JOURNAL OF HEPATOLOGY 79.3(2023):14. |
入库方式： OAI收割
来源：上海药物研究所
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