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Article

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

1
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
2
Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266237, China
*
Author to whom correspondence should be addressed.
Academic Editor: Beatriz Merino
Received: 6 November 2021 / Revised: 26 November 2021 / Accepted: 26 November 2021 / Published: 1 December 2021
(This article belongs to the Special Issue Fat Diets and Metabolic Diseases)
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. View Full-Text
Keywords: high-fat diets; FXR; lipid metabolism; ER stress; MAPK high-fat diets; FXR; lipid metabolism; ER stress; MAPK
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MDPI and ACS Style

Du, J.; Xiang, X.; Xu, D.; Zhang, J.; Fang, W.; Xu, W.; Mai, K.; Ai, Q. 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. Nutrients 2021, 13, 4343. https://0-doi-org.brum.beds.ac.uk/10.3390/nu13124343

AMA Style

Du J, Xiang X, Xu D, Zhang J, Fang W, Xu W, Mai K, Ai Q. 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. Nutrients. 2021; 13(12):4343. https://0-doi-org.brum.beds.ac.uk/10.3390/nu13124343

Chicago/Turabian Style

Du, Jianlong, Xiaojun Xiang, Dan Xu, Junzhi Zhang, Wei Fang, Wei Xu, Kangsen Mai, and Qinghui Ai. 2021. "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" Nutrients 13, no. 12: 4343. https://0-doi-org.brum.beds.ac.uk/10.3390/nu13124343

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