Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis
Abstract All‐trans retinoic acid (AtRA) is an active metabolite of vitamin A that influences many biological processes in development, differentiation, and metabolism. AtRA functions through activation of retinoid acid receptors (RARs). AtRA is shown to ameliorate hepatic steatosis, but the underlyi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Health/LWW
2022-10-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.2049 |
| _version_ | 1797935252385038336 |
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| author | Fathima N. Cassim Bawa Yanyong Xu Raja Gopoju Noel‐Marie Plonski Amy Shiyab Shuwei Hu Shaoru Chen Yingdong Zhu Kavita Jadhav Takhar Kasumov Yanqiao Zhang |
| author_facet | Fathima N. Cassim Bawa Yanyong Xu Raja Gopoju Noel‐Marie Plonski Amy Shiyab Shuwei Hu Shaoru Chen Yingdong Zhu Kavita Jadhav Takhar Kasumov Yanqiao Zhang |
| author_sort | Fathima N. Cassim Bawa |
| collection | DOAJ |
| description | Abstract All‐trans retinoic acid (AtRA) is an active metabolite of vitamin A that influences many biological processes in development, differentiation, and metabolism. AtRA functions through activation of retinoid acid receptors (RARs). AtRA is shown to ameliorate hepatic steatosis, but the underlying mechanism is not well understood. In this study, we investigated the role of hepatocyte RAR alpha (RARα) in mediating the effect of AtRA on hepatosteatosis in mice. Hepatocyte‐specific Rarα−/− (L‐Rarα−/−) mice and their control mice were fed a chow diet, high‐fat diet (HFD), or a high‐fat/cholesterol/fructose (HFCF) diet. Some of the mice were also treated with AtRA. Loss of hepatocyte RARα‐induced hepatosteatosis in chow‐fed aged mice and HFD‐fed mice. AtRA prevented and reversed HFCF diet–induced obesity and hepatosteatosis in the control mice but not in L‐Rarα−/− mice. Furthermore, AtRA reduced hepatocyte fatty acid uptake and lipid droplet formation, dependent on hepatocyte RARα. Our data suggest that hepatocyte RARα plays an important role in preventing hepatosteatosis and mediates AtRA's effects on diet‐induced hepatosteatosis. |
| first_indexed | 2024-04-10T18:11:28Z |
| format | Article |
| id | doaj.art-694b54558d4041fab6f981560f167922 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:11:28Z |
| publishDate | 2022-10-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-694b54558d4041fab6f981560f1679222023-02-02T10:46:17ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2022-10-016102665267510.1002/hep4.2049Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosisFathima N. Cassim Bawa0Yanyong Xu1Raja Gopoju2Noel‐Marie Plonski3Amy Shiyab4Shuwei Hu5Shaoru Chen6Yingdong Zhu7Kavita Jadhav8Takhar Kasumov9Yanqiao Zhang10School of Biomedical Sciences Kent State University Kent Kent Ohio USADepartment of Integrative Medical Sciences Northeast Ohio Medical University Rootstown Ohio USADepartment of Integrative Medical Sciences Northeast Ohio Medical University Rootstown Ohio USASchool of Biomedical Sciences Kent State University Kent Kent Ohio USASchool of Biomedical Sciences Kent State University Kent Kent Ohio USADepartment of Integrative Medical Sciences Northeast Ohio Medical University Rootstown Ohio USADepartment of Integrative Medical Sciences Northeast Ohio Medical University Rootstown Ohio USASchool of Biomedical Sciences Kent State University Kent Kent Ohio USASchool of Biomedical Sciences Kent State University Kent Kent Ohio USADepartment of Pharmaceutical Sciences Northeast Ohio Medical University Rootstown Ohio USADepartment of Integrative Medical Sciences Northeast Ohio Medical University Rootstown Ohio USAAbstract All‐trans retinoic acid (AtRA) is an active metabolite of vitamin A that influences many biological processes in development, differentiation, and metabolism. AtRA functions through activation of retinoid acid receptors (RARs). AtRA is shown to ameliorate hepatic steatosis, but the underlying mechanism is not well understood. In this study, we investigated the role of hepatocyte RAR alpha (RARα) in mediating the effect of AtRA on hepatosteatosis in mice. Hepatocyte‐specific Rarα−/− (L‐Rarα−/−) mice and their control mice were fed a chow diet, high‐fat diet (HFD), or a high‐fat/cholesterol/fructose (HFCF) diet. Some of the mice were also treated with AtRA. Loss of hepatocyte RARα‐induced hepatosteatosis in chow‐fed aged mice and HFD‐fed mice. AtRA prevented and reversed HFCF diet–induced obesity and hepatosteatosis in the control mice but not in L‐Rarα−/− mice. Furthermore, AtRA reduced hepatocyte fatty acid uptake and lipid droplet formation, dependent on hepatocyte RARα. Our data suggest that hepatocyte RARα plays an important role in preventing hepatosteatosis and mediates AtRA's effects on diet‐induced hepatosteatosis.https://doi.org/10.1002/hep4.2049 |
| spellingShingle | Fathima N. Cassim Bawa Yanyong Xu Raja Gopoju Noel‐Marie Plonski Amy Shiyab Shuwei Hu Shaoru Chen Yingdong Zhu Kavita Jadhav Takhar Kasumov Yanqiao Zhang Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis Hepatology Communications |
| title | Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis |
| title_full | Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis |
| title_fullStr | Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis |
| title_full_unstemmed | Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis |
| title_short | Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis |
| title_sort | hepatic retinoic acid receptor alpha mediates all trans retinoic acid s effect on diet induced hepatosteatosis |
| url | https://doi.org/10.1002/hep4.2049 |
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