热门
Fibroblast Growth Factor 21 Is Regulated by the IRE1 alpha-XBP1 Branch of the Unfolded Protein Response and Counteracts Endoplasmic Reticulum Stress-induced Hepatic Steatosis
文献类型：期刊论文
| 作者 | Jiang, Shan; Yan, Cheng; Fang, Qi-chen; Shao, Meng-le; Zhang, Yong-liang; Liu, Yang; Deng, Yi-ping; Shan, Bo; Liu, Jing-qi; Li, Hua-ting |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2014 |
| 卷号 | 289期号:43页码:29751-29765 |
| 关键词 | ER Stress Fibroblast Growth Factor (FGF) Hepatocyte Liver Metabolism Unfolded Protein Response (UPR) |
| 通讯作者 | Liu, Y (reprint author), Chinese Acad Sci, Key Lab Nutr, 294 Tai Yuan Rd, Shanghai 200031, Peoples R China. |
| 英文摘要 | Background: Although both are involved in metabolic homeostasis, the interconnection between ER stress and FGF21 remains incompletely understood. Results: Directly up-regulated by the IRE1-XBP1 pathway, FGF21 could alleviate ER stress-induced liver steatosis. Conclusion: FGF21 acts as a metabolic effector of the UPR program, exerting feedback effects upon lipid metabolism. Significance: These findings reveal a regulatory mechanism linking FGF21 actions to metabolic ER stress. Endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR) and represents a critical mechanism that underlies metabolic dysfunctions. Fibroblast growth factor 21 (FGF21), a hormone that is predominantly secreted by the liver, exerts a broad range of effects upon the metabolism of carbohydrates and lipids. Although increased circulating levels of FGF21 have been documented in animal models and human subjects with obesity and nonalcoholic fatty liver disease, the functional interconnections between metabolic ER stress and FGF21 are incompletely understood. Here, we report that increased ER stress along with the simultaneous elevation of FGF21 expression were associated with the occurrence of nonalcoholic fatty liver disease both in diet-induced obese mice and human patients. Intraperitoneal administration of the ER stressor tunicamycin in mice resulted in hepatic steatosis, accompanied by activation of the three canonical UPR branches and increased the expression of FGF21. Furthermore, the IRE1-XBP1 pathway of the UPR could directly activate the transcriptional expression of Fgf21. Administration of recombinant FGF21 in mice alleviated tunicamycin-induced liver steatosis, in parallel with reduced eIF2-ATF4-CHOP signaling. Taken together, these results suggest that FGF21 is an integral physiological component of the cellular UPR program, which exerts beneficial feedback effects upon lipid metabolism through counteracting ER stress. |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | FATTY LIVER-DISEASE ; ER STRESS ; TRANSCRIPTION FACTOR ; INSULIN SENSITIVITY ; PPAR-ALPHA ; METABOLIC REGULATOR ; ENERGY-EXPENDITURE ; MESSENGER-RNA ; BETA-KLOTHO ; FGF21 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000344370800023 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/272]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Jiang, Shan,Yan, Cheng,Fang, Qi-chen,et al. Fibroblast Growth Factor 21 Is Regulated by the IRE1 alpha-XBP1 Branch of the Unfolded Protein Response and Counteracts Endoplasmic Reticulum Stress-induced Hepatic Steatosis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(43):29751-29765. |
| APA | Jiang, Shan.,Yan, Cheng.,Fang, Qi-chen.,Shao, Meng-le.,Zhang, Yong-liang.,...&Jia, Wei-ping.(2014).Fibroblast Growth Factor 21 Is Regulated by the IRE1 alpha-XBP1 Branch of the Unfolded Protein Response and Counteracts Endoplasmic Reticulum Stress-induced Hepatic Steatosis.JOURNAL OF BIOLOGICAL CHEMISTRY,289(43),29751-29765. |
| MLA | Jiang, Shan,et al."Fibroblast Growth Factor 21 Is Regulated by the IRE1 alpha-XBP1 Branch of the Unfolded Protein Response and Counteracts Endoplasmic Reticulum Stress-induced Hepatic Steatosis".JOURNAL OF BIOLOGICAL CHEMISTRY 289.43(2014):29751-29765. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。