He Lingjie, Zhang Yupeng, Cao Quanquan, Shan Hongying, Zong Jiali, Feng Lin, Jiang Weidan, Wu Pei, Zhao Juan, Liu Haifeng, Jiang Jun
College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
Antioxidants (Basel). 2024 Jul 4;13(7):808. doi: 10.3390/antiox13070808.
Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation, affecting physiological and pathological processes. Fatty liver disease associated with metabolic dysfunction is a common pathological condition in aquaculture. However, the exact role and mechanism of ferroptosis in its pathogenesis and progression remains unclear. In this study, an experiment was conducted using different dietary lipid levels in the feeding of largemouth bass () for 11 weeks. The results revealed that the growth performance and whole-body protein content significantly increased with the elevation of dietary lipid levels up to 12%. The activities of antioxidant enzymes as well as the content of GSH (glutathione) in the liver initially increased but later declined as the lipid levels increased; the contents of MDA (malondialdehyde) and GSSG (oxidized glutathione) demonstrated an opposite trend. Moreover, elevating lipid levels in the diet significantly increased liver Fe content, as well as the expressions of TF (Transferrin), TFR (Transferrin receptor), ACSL4 (acyl-CoA synthetase long-chain family member 4), LPCAT3 (lysophosphatidylcholine acyltransferase 3), and LOX12 (Lipoxygenase-12), while decreasing the expressions of GPX4 (glutathione peroxidase 4) and SLC7A11 (Solute carrier family 7 member 11). In conclusion, the optimal lipid level is 12.2%, determined by WG-based linear regression. Excess lipid-level diets can up-regulate the ACSL4/LPCAT3/LOX12 axis, induce hepatic oxidative stress and cell death through a ferroptotic-like program, and decrease growth performance.
铁死亡是一种由铁依赖性脂质过氧化作用所表征的程序性细胞死亡形式，影响生理和病理过程。与代谢功能障碍相关的脂肪肝疾病是水产养殖中常见的病理状况。然而，铁死亡在其发病机制和进展中的确切作用和机制仍不清楚。在本研究中，使用不同的日粮脂质水平对大口黑鲈（）进行了为期11周的投喂实验。结果表明，日粮脂质水平升高至12%时，生长性能和鱼体蛋白质含量显著增加。肝脏中抗氧化酶活性以及谷胱甘肽（GSH）含量起初随着脂质水平升高而增加，但随后下降；丙二醛（MDA）和氧化型谷胱甘肽（GSSG）含量呈现相反趋势。此外，日粮中脂质水平升高显著增加了肝脏铁含量，以及转铁蛋白（TF）、转铁蛋白受体（TFR）、酰基辅酶A合成酶长链家族成员4（ACSL4）、溶血磷脂酰胆碱酰基转移酶3（LPCAT3）和脂氧合酶-12（LOX12）的表达，同时降低了谷胱甘肽过氧化物酶4（GPX4）和溶质载体家族7成员11（SLC7A11）的表达。总之，基于增重的线性回归确定最佳脂质水平为12.2%。脂质水平过高的日粮会上调ACSL4/LPCAT3/LOX12轴，通过类似铁死亡的程序诱导肝脏氧化应激和细胞死亡，并降低生长性能。
