水生生物学报2026，Vol.50Issue(9)：118-131,14.DOI:10.3724/1000-3207.2026.2026.0191
α-酮戊二酸代谢紊乱介导棕榈酸诱导斑马鱼肝脏脂肪异常沉积的机制研究
MECHANISM STUDY OF α-KETOGLUTARATE METABOLISM DISTURBANCE MEDIATES PALMITIC ACID INDUCED ABNORMAL HEPATIC LIPID DEPOSITION IN ZEBRAFISH(DANIO RERIO)
摘要
Abstract
To elucidate the specific molecular mechanisms by which α-ketoglutarate(AKG)regulates fat metabolism in zebrafish,this study demonstrated that oral administration of palm oil feed or ex vivo incubation with palmitic acid(PA)reduced the expression of AKG-metabolism-related genes in zebrafish livers or hepatocytes,thereby decreasing AKG levels.This study revealed that feeding palm oil in vivo or incubation with exogenous palmitic acid(PA)reduced the expression of AKG metabolism-related genes in zebrafish livers or hepatocytes,thereby decreasing AKG levels.Further experiments demonstrated that exogenous supplementation of AKG alleviates PA-induced AKG metabolic disturbances while modulating the expression of peroxisome proliferator-activated receptors(PPARs),thereby promot-ing fatty acid β-oxidation,inhibiting lipogenesis,and reducing lipid deposition.Conversely,inhibition of endogenous AKG synthesis using glutamate dehydrogenase inhibitor R162 suppressed fatty acid β-oxidation,enhanced lipogenesis,and induced hepatic lipid deposition.Additionally,PA-induced abnormal lipid deposition was associated with aberrant activation of the mTORC1 signaling pathway,and exogenous AKG supplementation effectively inhibited this activa-tion.In conclusion,feeding palm oil may induce AKG metabolic disturbances,activate the mTORC1 signaling path-way,alter PPARs expression,subsequently inhibit fatty acid β-oxidation,promote lipogenesis,and ultimately lead to hepatic lipid deposition in zebrafish.These findings provides a theoretical foundation for understanding how AKG regulateslipid metabolism in fish and identify potential regulatory targets for the efficient utilization of palm oil feeds.关键词
植物油/棕榈酸/α-酮戊二酸/脂质沉积/代谢紊乱/斑马鱼Key words
Vegetable oil/Palmitic acid/α-ketoglutarate/Lipid deposition/Metabolism disturbance/Zebrafish分类
农业科技引用本文复制引用
李修文,赵增琦,李宝林,温顺浪,武子贤,于翰杰,麦康森,艾庆辉..α-酮戊二酸代谢紊乱介导棕榈酸诱导斑马鱼肝脏脂肪异常沉积的机制研究[J].水生生物学报,2026,50(9):118-131,14.基金项目
国家自然科学基金-国际(地区)合作与交流项目(32320103012) （地区）
国家自然科学基金-山东省联合基金(U2106232) （U2106232）
山东省泰山学者攀登专家项目(tspd20240804)资助[Supported by the National Natural Science Foundation of China-International(Regional)Cooperation and Exchange Program(32320103012) （tspd20240804）
the National Natural Science Foundation of China-Shandong Provincial Joint Fund(U2106232) （U2106232）
the Shandong Taishan Scholar Climbing Expert Program(tspd20240804)] （tspd20240804）
