NDRG2 regulates milkfatbiosynthesis by targeting the AMPK/SREBP1 axis in bovine mammary epithelial cells

Milk fat serves as the primary energy source for both humans and animals, playing a pivotal role in various metabolic and physiological processes. N-myc downstream regulated gene 2 (NDRG2), a member of the NDRG family, is closely involved in cellular proliferation and differentiation. However, the specific role of NDRG2 in milk fat synthesis within bovine mammary epithelial cells (BMECs), as well as its underlying molecular mechanisms, remains unclear. RNA sequencing of BMECs from low-fat and high-fat dairy cows revealed 247 up-regulated genes and 258 down-regulated genes. Among these, NDRG2 may play an important role in the milk fat synthesis in BMECs. Overexpression of NDRG2 significantly enhanced milk fat synthesis and the expression of genes involved in fatty acid synthesis, activation, and transcriptional regulation in BMECs. Conversely, NDRG2 inhibition notably reduced milk fat synthesis in these cells. Further mechanistic investigations demonstrated that NDRG2 overexpression suppressed the AMPK/SREBP1 axis, thereby facilitating milk fat synthesis in BMECs. Additionally, NDRG2 was found to interact with ACC1, and its overexpression promoted milk fat synthesis through this interaction. These findings establish NDRG2 as a potential target for enhancing milk fat production in dairy cows.