Salidroside protects bovine hepatocytes against fatty acid–induced lipid accumulation and inflammation by activating AMPK/SIRT1 pathway

作者：Jinxia Li, Chenchen Zhao, Ke Zu, Zipei Fan, Dandan Qi, Fanrong Kong, Menglin Liu, Jie Gao, Enzhu Li, Wenwen Gao, Xiliang Du, Yuxiang Song, Guowen Liu, Xinwei Li, Haihua Feng, Lin Lei · 发表于：Journal of Dairy Science · 年份：2025 · DOI：10.3168/jds.2024-26083 · 被引用次数：5 · 研究领域：Medicinal Plants and Bioactive Compounds、Lipid metabolism and disorders、Liver Disease Diagnosis and Treatment

Fat mobilization and elevated circulating levels of nonesterified fatty acids (NEFA) resulting from severe negative energy balance (NEB) are the major causes of hepatic lipid accumulation and inflammation in dairy cows during the transition period. However, there is a lack of promising therapeutic agents to control NEFA-induced lipotoxicity in the liver of dairy cows. Thus, the objective of this study was to investigate the effects of salidroside (Sal), the principal bioactive component of Rhodiola, on NEFA-induced lipotoxicity in bovine hepatocytes, as well as the underlying molecular mechanisms. Bovine hepatocytes were isolated from 5 healthy Holstein female newborn calves (1 d of age, 30-40 kg, fasting) and treated with NEFA (1.2 mM), Sal (0, 5, 25, 50, 100, or 200 μM), or both for 12 h. To elucidate the role of the AMP-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) signaling axis, hepatocytes were additionally treated with inhibitors against AMPK or SIRT1. The results showed that Sal treatment significantly alleviated NEFA-induced increases in triacylglycerol (TAG) content, protein abundance of sterol regulatory element-binding protein 1c (SREBP-1c) and mRNA levels of SREBP1 and acetyl-CoA carboxylase 1 (ACACA). Furthermore, Sal alleviated the downregulation of peroxisome proliferator-activated receptor α (PPARA) protein abundance and mRNA levels of PPARA and carnitine palmitoyltransferase 1A (CPT1A). In addition, Sal treatment markedly decreased N...