Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis
ObjectiveThe aim of this study was to investigate whether the nuclear receptor farnesoid X receptor (FXR) could regulate FNDC5/Irisin expression and the role of Irisin in hyperlipidemia and atherosclerosis in ApoE-/- mice.Methods and ResultsWe treated primary human hepatocytes, HepG2 cells, and Rhes...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00548/full |
| id |
doaj-7943583ff535430187f1f89165526aab |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hong Li Hong Li Jing Shen Jing Shen Tong Wu Tong Wu Jiangying Kuang Jiangying Kuang Qinhui Liu Shihai Cheng Shihai Cheng Shiyun Pu Shiyun Pu Lei Chen Lei Chen Rui Li Rui Li Yanping Li Yanping Li Min Zou Zhiyong Zhang Wei Jiang Aijuan Qu Jinhan He Jinhan He |
| spellingShingle |
Hong Li Hong Li Jing Shen Jing Shen Tong Wu Tong Wu Jiangying Kuang Jiangying Kuang Qinhui Liu Shihai Cheng Shihai Cheng Shiyun Pu Shiyun Pu Lei Chen Lei Chen Rui Li Rui Li Yanping Li Yanping Li Min Zou Zhiyong Zhang Wei Jiang Aijuan Qu Jinhan He Jinhan He Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis Frontiers in Pharmacology FNDC5/Irisin FXR hyperlipidemia atherosclerosis ApoE-/- |
| author_facet |
Hong Li Hong Li Jing Shen Jing Shen Tong Wu Tong Wu Jiangying Kuang Jiangying Kuang Qinhui Liu Shihai Cheng Shihai Cheng Shiyun Pu Shiyun Pu Lei Chen Lei Chen Rui Li Rui Li Yanping Li Yanping Li Min Zou Zhiyong Zhang Wei Jiang Aijuan Qu Jinhan He Jinhan He |
| author_sort |
Hong Li |
| title |
Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis |
| title_short |
Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis |
| title_full |
Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis |
| title_fullStr |
Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis |
| title_full_unstemmed |
Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis |
| title_sort |
irisin is controlled by farnesoid x receptor and regulates cholesterol homeostasis |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Pharmacology |
| issn |
1663-9812 |
| publishDate |
2019-05-01 |
| description |
ObjectiveThe aim of this study was to investigate whether the nuclear receptor farnesoid X receptor (FXR) could regulate FNDC5/Irisin expression and the role of Irisin in hyperlipidemia and atherosclerosis in ApoE-/- mice.Methods and ResultsWe treated primary human hepatocytes, HepG2 cells, and Rhesus macaques with FXR agonist (CDCA, GW4064, and ivermectin). FNDC5 expression was highly induced by CDCA and GW4064 in hepatocytes, HepG2 cells, and the circulating level of Irisin increased in Rhesus macaques. Luciferase reporter and CHIP assays were used to determine whether FXR could regulate FNDC5 promoter activity. Irisin-ApoE-/- and ApoE-/- mice were used to study the metabolic function of Irisin in dyslipidemia and atherosclerosis. Irisin-ApoE-/- mice showed improved hyperlipidemia and alleviated atherosclerosis as compared with ApoE-/- mice. Irisin upregulated the expression of Abcg5/Abcg8 in liver and intestine, which increased the transport of biliary cholesterol and fecal cholesterol output.ConclusionActivation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. |
| topic |
FNDC5/Irisin FXR hyperlipidemia atherosclerosis ApoE-/- |
| url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00548/full |
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doaj-7943583ff535430187f1f89165526aab2020-11-25T01:34:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-05-011010.3389/fphar.2019.00548454821Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol HomeostasisHong Li0Hong Li1Jing Shen2Jing Shen3Tong Wu4Tong Wu5Jiangying Kuang6Jiangying Kuang7Qinhui Liu8Shihai Cheng9Shihai Cheng10Shiyun Pu11Shiyun Pu12Lei Chen13Lei Chen14Rui Li15Rui Li16Yanping Li17Yanping Li18Min Zou19Zhiyong Zhang20Wei Jiang21Aijuan Qu22Jinhan He23Jinhan He24Department of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, Molecular Medicine Research Center – Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaObjectiveThe aim of this study was to investigate whether the nuclear receptor farnesoid X receptor (FXR) could regulate FNDC5/Irisin expression and the role of Irisin in hyperlipidemia and atherosclerosis in ApoE-/- mice.Methods and ResultsWe treated primary human hepatocytes, HepG2 cells, and Rhesus macaques with FXR agonist (CDCA, GW4064, and ivermectin). FNDC5 expression was highly induced by CDCA and GW4064 in hepatocytes, HepG2 cells, and the circulating level of Irisin increased in Rhesus macaques. Luciferase reporter and CHIP assays were used to determine whether FXR could regulate FNDC5 promoter activity. Irisin-ApoE-/- and ApoE-/- mice were used to study the metabolic function of Irisin in dyslipidemia and atherosclerosis. Irisin-ApoE-/- mice showed improved hyperlipidemia and alleviated atherosclerosis as compared with ApoE-/- mice. Irisin upregulated the expression of Abcg5/Abcg8 in liver and intestine, which increased the transport of biliary cholesterol and fecal cholesterol output.ConclusionActivation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis.https://www.frontiersin.org/article/10.3389/fphar.2019.00548/fullFNDC5/IrisinFXRhyperlipidemiaatherosclerosisApoE-/- |