FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets
High-fat diets induced abnormal lipid accumulation in the liver of cultured fish that caused body damage and diseases. The purpose of this research was to investigate the role and mechanism of farnesoid X receptor (FXR) in regulating lipid metabolism and to determine how high-fat diets affect FXR ex...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/13/12/4343 |
| _version_ | 1797501876693893120 |
|---|---|
| author | Jianlong Du Xiaojun Xiang Dan Xu Junzhi Zhang Wei Fang Wei Xu Kangsen Mai Qinghui Ai |
| author_facet | Jianlong Du Xiaojun Xiang Dan Xu Junzhi Zhang Wei Fang Wei Xu Kangsen Mai Qinghui Ai |
| author_sort | Jianlong Du |
| collection | DOAJ |
| description | High-fat diets induced abnormal lipid accumulation in the liver of cultured fish that caused body damage and diseases. The purpose of this research was to investigate the role and mechanism of farnesoid X receptor (FXR) in regulating lipid metabolism and to determine how high-fat diets affect FXR expression in large yellow croakers. The results showed that ligand-meditated FXR-activation could prevent abnormal lipid accumulation in the liver and hepatocytes of large yellow croakers. FXR activation increased the expression of lipid catabolism-related genes while decreasing the expression of lipogenesis-related genes. Further investigation found that the promoter activity of proliferator-activated receptor α (PPARα) could be increased by croaker FXR. Through the influence of SHP on LXR, FXR indirectly decreased the promoter activity of sterol regulatory element binding protein 1 (SREBP1) in large yellow croakers. Furthermore, the findings revealed that endoplasmic reticulum (ER)-stress-induced-activation of JNK and P38 MAPK participated in the reduction of FXR induced by high-fat diets. Then, hepatocyte nuclear factor 1α (HNF1α) was confirmed to be an FXR regulator in large yellow croaker, and it was reduced by high-fat diets and ER stress. In addition, co-expression of c-Jun with HNF1α inhibited the effect of HNF1α on FXR promoter, and suppression of P38 MAPK could relieve the HNF1α expression reduction caused by ER stress activation. In summary, the present study showed that FXR mediated lipid metabolism can prevent abnormal lipid accumulation through regulating PPARα and SREBP1 in large yellow croakers, while high-fat diets can suppress FXR expression by ER stress mediated-activation of JNK and P38 MAPK pathways. This research could benefit the study of FXR functions in vertebrate evolution and the development of therapy or preventative methods for nutrition-related disorders. |
| first_indexed | 2024-03-10T03:24:55Z |
| format | Article |
| id | doaj.art-f2bfa255107540f482072f0b4304214f |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T03:24:55Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-f2bfa255107540f482072f0b4304214f2023-11-23T09:56:26ZengMDPI AGNutrients2072-66432021-12-011312434310.3390/nu13124343FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat DietsJianlong Du0Xiaojun Xiang1Dan Xu2Junzhi Zhang3Wei Fang4Wei Xu5Kangsen Mai6Qinghui Ai7Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao 266003, ChinaHigh-fat diets induced abnormal lipid accumulation in the liver of cultured fish that caused body damage and diseases. The purpose of this research was to investigate the role and mechanism of farnesoid X receptor (FXR) in regulating lipid metabolism and to determine how high-fat diets affect FXR expression in large yellow croakers. The results showed that ligand-meditated FXR-activation could prevent abnormal lipid accumulation in the liver and hepatocytes of large yellow croakers. FXR activation increased the expression of lipid catabolism-related genes while decreasing the expression of lipogenesis-related genes. Further investigation found that the promoter activity of proliferator-activated receptor α (PPARα) could be increased by croaker FXR. Through the influence of SHP on LXR, FXR indirectly decreased the promoter activity of sterol regulatory element binding protein 1 (SREBP1) in large yellow croakers. Furthermore, the findings revealed that endoplasmic reticulum (ER)-stress-induced-activation of JNK and P38 MAPK participated in the reduction of FXR induced by high-fat diets. Then, hepatocyte nuclear factor 1α (HNF1α) was confirmed to be an FXR regulator in large yellow croaker, and it was reduced by high-fat diets and ER stress. In addition, co-expression of c-Jun with HNF1α inhibited the effect of HNF1α on FXR promoter, and suppression of P38 MAPK could relieve the HNF1α expression reduction caused by ER stress activation. In summary, the present study showed that FXR mediated lipid metabolism can prevent abnormal lipid accumulation through regulating PPARα and SREBP1 in large yellow croakers, while high-fat diets can suppress FXR expression by ER stress mediated-activation of JNK and P38 MAPK pathways. This research could benefit the study of FXR functions in vertebrate evolution and the development of therapy or preventative methods for nutrition-related disorders.https://www.mdpi.com/2072-6643/13/12/4343high-fat dietsFXRlipid metabolismER stressMAPK |
| spellingShingle | Jianlong Du Xiaojun Xiang Dan Xu Junzhi Zhang Wei Fang Wei Xu Kangsen Mai Qinghui Ai FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets Nutrients high-fat diets FXR lipid metabolism ER stress MAPK |
| title | FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets |
| title_full | FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets |
| title_fullStr | FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets |
| title_full_unstemmed | FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets |
| title_short | FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (<i>Larimichthys crocea</i>) Fed High Fat Diets |
| title_sort | fxr a key regulator of lipid metabolism is inhibited by er stress mediated activation of jnk and p38 mapk in large yellow croakers i larimichthys crocea i fed high fat diets |
| topic | high-fat diets FXR lipid metabolism ER stress MAPK |
| url | https://www.mdpi.com/2072-6643/13/12/4343 |
| work_keys_str_mv | AT jianlongdu fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT xiaojunxiang fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT danxu fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT junzhizhang fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT weifang fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT weixu fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT kangsenmai fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets AT qinghuiai fxrakeyregulatoroflipidmetabolismisinhibitedbyerstressmediatedactivationofjnkandp38mapkinlargeyellowcroakersilarimichthyscroceaifedhighfatdiets |