The hepatic expression status of hepatocyte nuclear factor 4α in subclinical and clinical ketotic dairy cows and its impact on lipid metabolism in hepatocytes

作者：Meng Chen, Li Wang, Lin Lei, Xiliang Du, Juan J. Loor, Shilin Mei, Chenxu Li, Yuting Yang, Wenwen Gao, Yuxiang Song, Xinwei Li, Guowen Liu, Zhiyuan Fang · 发表于：Journal of Dairy Science · 年份：2025 · DOI：10.3168/jds.2025-26548 · 被引用次数：4 · 研究领域：Reproductive Physiology in Livestock、Liver Disease Diagnosis and Treatment、Genetic and phenotypic traits in livestock

Due to sustained lipolysis, excessive nonesterified fatty acid (NEFA) concentrations are a common pathological factor of ketosis in peripartal cows. The NEFA provide an energy source to the liver during the transition period, but when in excess they can induce hepatic steatosis and liver dysfunction. In nonruminants, hepatocyte nuclear factor 4α (HNF4α) is involved in lipid metabolism processes in the liver. However, it is unclear whether HNF4α regulates hepatic lipid metabolism and function in cows with subclinical (SCK) and clinical ketosis (CK). Thus, the objective of this study was to investigate the expression status of the HNF4α in the liver of SCK and CK cows and its effects on lipid metabolism and cell function in hepatocytes. Liver and blood samples were collected from control cows (n = 15), cows with SCK (n = 15) and cows with CK (n = 15). To determine the effects of NEFA on lipid metabolism and cell function in vitro, hepatocytes isolated from calves were (1) treated with 0, 0.3, 0.6, or 1.2 mM NEFA for 12 h; (2) transfected with small interfering RNA for control (si-control) or si-HNF4A, or pCMV-EGFP or pCMV-EGFP-HNF4A for 48 h; (3) transfected with si-control or si-HNF4A, or pCMV-EGFP or pCMV-EGFP-HNF4A for 36 h, and then treated with 1.2 mM NEFA for 12 h. Results revealed that CK cows had hepatic steatosis and liver dysfunction. The protein abundance of HNF4α and its downstream targets carboxylesterase 1 (CES1) and CES2 as well as the mRNA abundance of CES1 and ...