KLF4 promotes milk fat synthesis by regulating the PI3K-AKT-mTOR pathway and targeting FASN activation in bovine mammary epithelial cells

Hong-Yu Wu; Zhong-Hao Ji; Wen-Yin Xie; Hai-Xiang Guo; Yi Zheng; Wei Gao; Bao Yuan

doi:10.1016/j.isci.2024.109850

KLF4 promotes milk fat synthesis by regulating the PI3K-AKT-mTOR pathway and targeting FASN activation in bovine mammary epithelial cells

iScience. 2024 Apr 30;27(6):109850. doi: 10.1016/j.isci.2024.109850. eCollection 2024 Jun 21.

Authors

Hong-Yu Wu^{1

2}, Zhong-Hao Ji^{1

3}, Wen-Yin Xie¹, Hai-Xiang Guo¹, Yi Zheng¹, Wei Gao¹, Bao Yuan¹

Affiliations

¹ Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, China.
² Jilin Academy of Agricultural Sciences, Jilin 132101, China.
³ Department of Basic Medicine, Changzhi Medical College, Changzhi 046000, Shanxi, China.

Abstract

Milk fat is an important indicator for evaluating the quality of cow's milk. In this study, we used bovine mammary epithelial cells (BMECs) to investigate the role and molecular mechanism of KLF4 in the regulation of milk fat synthesis. The results showed that KLF4 was more highly expressed in mammary tissues of high-fat cows compared with low-fat cows. KLF4 positively regulated the expression of genes related to milk fat synthesis in BMECs, increasing intracellular triglycerides content, and KLF4 promoted milk fat synthesis by activating the PI3K-AKT-mTOR signaling pathway. Furthermore, the results of animal experiments also confirmed that knockdown of KLF4 inhibited milk fat synthesis. In addition, yeast one-hybrid assays and dual-luciferase reporter gene assays confirmed that KLF4 directly targets and binds to the fatty acid synthase (FASN) promoter region to promote FASN transcription. These results demonstrate that KLF4 is a key transcription factor for milk fat synthesis in BMECs.

Keywords: animal food products; animal physiology; dairy cattle molecular biology; molecular biology.