Research
| Title： | Zinc-Mediated Deacetylation of Farnesoid X Receptor Activates the Adipose Triglyceride Lipase Pathway to Reduce Hepatic Lipid Accumulation and Enhance Lipolysis in Yellow Catfish |
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| First author： | Chen, Chuan; Liu, Xuebo; Wang, Jiawei; Wen, Xiaobo; Zhao, Huihong; Chen, Guanghui; Wu, Kun |
| Journal： | JOURNAL OF NUTRITION |
| Years： | 2025 |
| DOI： | 10.1016/j.tjnut.2025.03.012 |
| Abstract： | Background: High-fat diets (HFDs) can lead to excessive accumulation of lipids in the liver, leading to liver injury. Dietary zinc (Zn) has been shown to reduce HFD-induced lipid accumulation and improve lipid profiles in mammals, yet it remains unclear whether waterborne Zn maintains its lipid-lowering effects in osteichthyes. Objectives: This study aimed to elucidate the regulatory role of Zn in HFD-induced hepatic lipid accumulation in yellow catfish (Pelteo-bagrus fulvidraco) and its potential mechanisms. Methods: Yellow catfish were fed a control diet (11.21% lipid concentration), HFD (16.10% lipid concentration), or HFD combined with waterborne Zn exposure (0.2 mg/L) for 8 wk. Various biochemical, genetic, histologic, and molecular techniques were conducted to evaluate hepatic lipid deposition and lipid metabolism and determine protein interactions between silent information regulator (SIRT) 1 and farnesoid X receptor (FXR), as well as protein-gene interactions between FXR and adipose triglyceride lipase (ATGL). Results: HFD feeding significantly increased liver fat content and induced hepatic damage in yellow catfish, but concurrent exposure to waterborne Zn alleviated these detrimental effects. Zn treatment increased mRNA and protein concentrations of SIRT1 (mean f SEM; 97.19% f 11.67% and 83.25% f 28.60%, respectively) and FXR (163.90% f 24.60% and 24.90% f 11.12%, respectively) in yellow catfish liver (P < 0.05). Zn-activated FXR directly interacted with the promoter of ATGL, stimulating the expression of atgl (54.40% f 16.33%; P < 0.05) and facilitating the hydrolysis of triglycerides and lipid droplets. Furthermore, Zn reduced the acetylation concentration of FXR by SIRT1 deacetylation of FXR protein K167. Conclusions: The findings reveal that Zn protect against HFD-induced liver injury in yellow catfish by promoting the deacetylation of FXR protein K167 by SIRT1 and activating FXR, thereby promoting the transcriptional activation of ATGL to increase lipolysis. |
