{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:55:22Z","timestamp":1790787322858,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Fund for Distinguished Young Scholars of China","award":["31525024"],"award-info":[{"award-number":["31525024"]}]},{"name":"the Key Program of National Natural Science Foundation of China","award":["31830103"],"award-info":[{"award-number":["31830103"]}]},{"name":"the Scientific and Technological Innovation of Blue Granary","award":["2018YFD0900402"],"award-info":[{"award-number":["2018YFD0900402"]}]},{"name":"the Agriculture Research System of China","award":["CARS-47-11"],"award-info":[{"award-number":["CARS-47-11"]}]},{"name":"the Ten-thousand Talents Program","award":["2018-29"],"award-info":[{"award-number":["2018-29"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 \u03b1 (PPAR\u03b1) 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 1\u03b1 (HNF1\u03b1) 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 HNF1\u03b1 inhibited the effect of HNF1\u03b1 on FXR promoter, and suppression of P38 MAPK could relieve the HNF1\u03b1 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 PPAR\u03b1 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.<\/jats:p>","DOI":"10.3390\/nu13124343","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T02:40:02Z","timestamp":1638412802000},"page":"4343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (Larimichthys crocea) Fed High Fat Diets"],"prefix":"10.3390","volume":"13","author":[{"given":"Jianlong","family":"Du","sequence":"first","affiliation":[{"name":"Key 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Xiang","sequence":"additional","affiliation":[{"name":"Key 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Key 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Fang","sequence":"additional","affiliation":[{"name":"Key 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key 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, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangsen","family":"Mai","sequence":"additional","affiliation":[{"name":"Key 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, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Ai","sequence":"additional","affiliation":[{"name":"Key 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, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/j.1872-034X.2011.00824.x","article-title":"NASH: A global health problem","volume":"41","author":"Sanyal","year":"2011","journal-title":"Hepatol. 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