Peroxisome proliferator-activated receptor gamma is essential for stress adaptation by maintaining lipid homeostasis in female fish

文献类型： 外文期刊

第一作者： Wang, Xue

作者： Wang, Xue;Chen, Lingyun;Wu, Hongxia;Chen, Li-Qiao;Qiao, Fang;Luo, Yuan;Zhang, Mei-Ling;Du, Zhen-Yu;Ma, Qiang

作者机构：

关键词： pparg; Lipotoxicity; Oxidative stress; Environmental stress resistance; Zebrafish

期刊名称：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS （ 影响因子：5.228； 五年影响因子：5.545 ）

ISSN： 1388-1981

年卷期： 2022 年 1867 卷 7 期

页码：

收录情况： SCI

摘要： Reduction of lipid synthesis often causes free fatty acid (FFA) overload, resulting consequential oxidative stress and health damage. Environmental stresses also induce cellular oxidative stress in organisms. The functional peroxisome proliferator-activated receptor gamma (pparg) gene is essential for lipid synthesis and homeostatic lipid maintenance. However, the relationship between the pparg-mediated lipid synthesis and environmental stress adaptation awaits full elucidation. Here, we generated a pparg-knockout zebrafish model. The conversion of free fatty acids into triglycerides in the female pparg mutants was hampered by reduced esterification efficiency, thus induced lipotoxicity, as evidenced by high oxidative stress and damaged health in these mutants, which led to reduced resistance to cold, heat and ammonia nitrogen stresses. Activating pparg in the wild-type female fish via dietary supplementation with rosiglitazone (a pparg agonist), or reducing oxidative stress in the female pparg mutants via dietary supplementation with N-acetylcysteine (an antioxidant), or promoting mitochondrial fatty acid beta-oxidation in the female pparg mutants via dietary supplementation with L-carnitine, resulted in significantly reduced cellular injury, and improved environmental stress resistance. Collectively, our findings reveal that the regulative function of pparg in FFA esterification is important in stress resistance in female fish, and highlight the tight correlation existing between lipotoxicity and environmental adaptation.

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