CD36 molecule and AMP-activated protein kinase signaling drive docosahexaenoic acid-induced lipid remodeling in goat mammary epithelial cells

Goat milk is a vital component of China's dairy industry, renowned for its richness in lipids essential to human health. Polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (C22:6n-3, DHA), are particularly valuable for their integration into Phospholipids and triacylglycerols. While mammary cells can uptake and channel PUFAs into lipids for milk fat secretion, the broader functional effects of DHA within these cells remain unclear. This study demonstrated that DHA supplementation markedly altered levels of lipid subclasses in goat mammary epithelial cells (GMECs), as revealed by lipidomic analysis. DHA treatment significantly increased the levels of free DHA, alongside DHA-enriched triacylglycerols, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, thereby driving lipid remodeling in GMECs. Additionally, DHA modulated transcription of key fatty acid metabolism genes, such as SREBP1, FASD2, and FASN. Mechanistically, DHA supplementation activated the AMPK signaling pathway inhibiting fatty acid metabolism, and upregulated the expression of fatty acid transport gene-CD36 in GMECs. Knockdown or mutation of the fatty acid binding domain of CD36 diminished DHA-induced AMPK activation and transcriptional regulation of fatty acid metabolism genes in GMECs. In summary, DHA supplementation induces lipid remodeling in GMECs via the CD36-AMPK signaling axis, highlighting its potential to facilitate the development of DHA-enriched functional goat milk.

AMPK; CD36; DHA; Fatty acid metabolism; Lipid remodeling.