Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation
Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent metabolic disorder all over the world, and lipid metabolic disorders and inflammation are closely associated and contribute to the pathogenesis of NAFLD. Cholesterol 25-hydroxylase (Ch25h) and its product, 25-hydroxycholestero...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-04-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022030 |
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| _version_ | 1850128861367369728 |
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| author | Wang Yaqiong Zhang Jin Chen Jie Wang Dan Yu Yang Qiu Pei Wang Qiqi Zhao Wenbao Li Zhao Lei Ting |
| author_facet | Wang Yaqiong Zhang Jin Chen Jie Wang Dan Yu Yang Qiu Pei Wang Qiqi Zhao Wenbao Li Zhao Lei Ting |
| author_sort | Wang Yaqiong |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent metabolic disorder all over the world, and lipid metabolic disorders and inflammation are closely associated and contribute to the pathogenesis of NAFLD. Cholesterol 25-hydroxylase (Ch25h) and its product, 25-hydroxycholesterol (25-HC), play important roles in cholesterol homeostasis and inflammation, but whether Ch25h and 25-HC are involved in NAFLD remains uncertain. In this study, we use Ch25h knockout mice, hepatic cells and liver biopsies to explore the role of Ch25h and 25-HC in lipid metabolism and accumulation in liver, determine the molecular mechanism of lipid accumulation and inflammation influenced by Ch25h and 25-HC, and assess the regulatory effects of Ch25h and 25-HC on human NAFLD. Our results indicate that mice lacking Ch25h have normal cholesterol homeostasis with normal diet, but under the condition of high fat diet (HFD), the mice show higher total cholesterol and triglyceride in serum, and prone to hepatic steatosis. Ch25h deficiency reduces the cholesterol efflux regulated by liver X receptor α (LXRα), increases the synthesis of cholesterol mediated by sterol-regulatory element binding protein 2 (SREBP-2), and increases the activation of NLRP3 inflammasome, therefore promotes hepatic steatosis. Collectively, our data suggest that Ch25h and 25-HC play important roles in lipid metabolism and inflammation, thereby exerting anti-NAFLD functions. |
| format | Article |
| id | doaj-art-5d67f6731a7d47768058583d89932e4a |
| institution | OA Journals |
| issn | 1672-9145 |
| language | English |
| publishDate | 2022-04-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-5d67f6731a7d47768058583d89932e4a2025-08-20T02:33:09ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-04-015450451310.3724/abbs.202203020d259ccCh25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammationWang Yaqiong0Zhang Jin1Chen Jie2Wang Dan3Yu Yang4Qiu Pei5Wang Qiqi6Zhao Wenbao7Li Zhao8Lei Ting9["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China","Xi’an Blood Center, Xi’an 710061, China"]["Cardiovascular Research Center, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China, and"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China","Department of Pathology, Shannxi Provincial People’s Hospital, Xi’an 710068, China"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China"]["Cardiovascular Research Center, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China, and"]["Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China"]Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent metabolic disorder all over the world, and lipid metabolic disorders and inflammation are closely associated and contribute to the pathogenesis of NAFLD. Cholesterol 25-hydroxylase (Ch25h) and its product, 25-hydroxycholesterol (25-HC), play important roles in cholesterol homeostasis and inflammation, but whether Ch25h and 25-HC are involved in NAFLD remains uncertain. In this study, we use Ch25h knockout mice, hepatic cells and liver biopsies to explore the role of Ch25h and 25-HC in lipid metabolism and accumulation in liver, determine the molecular mechanism of lipid accumulation and inflammation influenced by Ch25h and 25-HC, and assess the regulatory effects of Ch25h and 25-HC on human NAFLD. Our results indicate that mice lacking Ch25h have normal cholesterol homeostasis with normal diet, but under the condition of high fat diet (HFD), the mice show higher total cholesterol and triglyceride in serum, and prone to hepatic steatosis. Ch25h deficiency reduces the cholesterol efflux regulated by liver X receptor α (LXRα), increases the synthesis of cholesterol mediated by sterol-regulatory element binding protein 2 (SREBP-2), and increases the activation of NLRP3 inflammasome, therefore promotes hepatic steatosis. Collectively, our data suggest that Ch25h and 25-HC play important roles in lipid metabolism and inflammation, thereby exerting anti-NAFLD functions.https://www.sciengine.com/doi/10.3724/abbs.2022030high fat dietLXRαNLRP3 inflammasomeCh25h25-HC |
| spellingShingle | Wang Yaqiong Zhang Jin Chen Jie Wang Dan Yu Yang Qiu Pei Wang Qiqi Zhao Wenbao Li Zhao Lei Ting Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation Acta Biochimica et Biophysica Sinica high fat diet LXRα NLRP3 inflammasome Ch25h 25-HC |
| title | Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation |
| title_full | Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation |
| title_fullStr | Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation |
| title_full_unstemmed | Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation |
| title_short | Ch25h and 25-HC prevent liver steatosis through regulation of cholesterol metabolism and inflammation |
| title_sort | ch25h and 25 hc prevent liver steatosis through regulation of cholesterol metabolism and inflammation |
| topic | high fat diet LXRα NLRP3 inflammasome Ch25h 25-HC |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022030 |
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