Intestinal farnesoid X receptor signaling controls hepatic fatty acid oxidation
文献类型：期刊论文
| 作者 | Lu, Dasheng1,2; Liu, Yameng3; Luo, Yuhong1; Zhao, Jie1; Feng, Chao2; Xue, Liming2; Xu, Jiale2; Wang, Qiong1; Yan, Tingting1; Xiao, Ping2 |
| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
 |
| 出版日期 | 2022-02-01 |
| 卷号 | 1867期号:2页码:13 |
| 关键词 | Fatty acid oxidation Acylcarnitines FXR FGF15/19 PGC1 alpha Transcriptomics Metabolomics |
| ISSN号 | 1388-1981 |
| DOI | 10.1016/j.bbalip.2021.159089 |
| 通讯作者 | Gonzalez, Frank J.(gonzalef@mail.nih.gov) ; Xie, Cen(xiecen@simm.ac.cn) |
| 英文摘要 | In addition to maintaining bile acid, cholesterol and glucose homeostasis, farnesoid X receptor (FXR) also regulates fatty acid beta-oxidation (FAO). To explore the different roles of hepatic and intestinal FXR in liver FAO, FAO-associated metabolites, including acylcarnitines and fatty acids, and FXR target gene mRNAs were profiled using an integrated metabolomic and transcriptomic analysis in control (Fxr(fl/fl)) , liver-specific Fxr-null (Fxr(Delta Hep)) and intestine-specific Fxr-null (Fxr(Delta)(IE)) mice, treated either with the FXR agonist obeticholic acid (OCA) or vehicle (VEH). Activation of FXR by OCA treatment significantly increased fatty acyl-CoA hydrolysis (Acot1) and decreased FAO-associated mRNAs in Fxr(fl/fl) mice, resulting in reduced levels of total acylcarnitines and relative accumulation of long/medium chain acylcarnitines and fatty acids in liver. Fxr(Delta Hep) mice responded to OCA treatment in a manner similar to Fxr(fl/fl) mice while Fxr(Delta)(IE) mice responded differently, thus illustrating that intestinal FXR plays a critical role in the regulation of hepatic FAO. A significant negative-correlation between intestinal FXR-FGF15 and hepatic CREB-PGC1A pathways was observed after both VEH and OCA treatment, suggesting that OCA-induced activation of the intestinal FXR-FGF15 axis downregulates hepatic PGC1 alpha signaling via inactivation of hepatic CREB, thus repressing FAO. This mechanism was confirmed in experiments based on human recombinant FGF19 treatment and intestinal Fgf15-null mice. This study revealed an important role for the intestinal FXR-FGF15 pathway in hepatic FAO repression. |
| WOS关键词 | FIBROBLAST GROWTH FACTOR-19 ; PPAR-ALPHA ; COACTIVATOR PGC-1 ; PGC-1-ALPHA ; METABOLISM ; IDENTIFICATION |
| 资助项目 | Na-tional Institutes of Health, National Cancer Institute, Center for Cancer Research[NIH U01 DK119702] ; National Natural Science Foundation of China[81872643] ; National Natural Science Foundation of China[91957116] ; Shanghai Municipal Science Foundation[18ZR1432200] ; Shanghai Rising-Star Program[20QA1411200] ; Shanghai Municipal Overseas High-End Talent Training of Public Health[GWTD2015S03] ; 3-year Action Program of Shanghai Municipal Government ; Shanghai Municipal Science andTechnology Major Project |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000729063500004 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299235]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gonzalez, Frank J.; Xie, Cen |
| 作者单位 | 1.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA 2.Shanghai Municipal Ctr Dis Control & Prevent, State Environm Protect Key Lab Environm Hlth Impa, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lu, Dasheng,Liu, Yameng,Luo, Yuhong,et al. Intestinal farnesoid X receptor signaling controls hepatic fatty acid oxidation[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,2022,1867(2):13. |
| APA | Lu, Dasheng.,Liu, Yameng.,Luo, Yuhong.,Zhao, Jie.,Feng, Chao.,...&Xie, Cen.(2022).Intestinal farnesoid X receptor signaling controls hepatic fatty acid oxidation.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,1867(2),13. |
| MLA | Lu, Dasheng,et al."Intestinal farnesoid X receptor signaling controls hepatic fatty acid oxidation".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS 1867.2(2022):13. |
入库方式： OAI收割
来源：上海药物研究所
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