CIDEA Regulates De Novo Fatty Acid Synthesis in Bovine Mammary Epithelial Cells by Targeting the AMPK/PPARγ Axis and Regulating SREBP1.

Abstract

Cell-death-inducing DNA fragmentation factor-α-like effector A (CIDEA) is a lipid-droplet-associated protein that helps to promote lipid metabolism in adipocytes of mice and humans. However, studies on the regulatory mechanism of CIDEA on lipid metabolism in the mammary glands of dairy cows are rare. Therefore, the role of CIDEA in bovine mammary epithelial cells (bMECs) was investigated in this study. The CIDEA expression levels in the mammary glands of high-fat-milk-producing cows were significantly higher compared to those in low-fat-milk-producing cows. Results of in vitro studies in bMECs showed that the inhibition of CIDEA inhibited the expression of fatty acid synthesis-related genes and triglyceride (TAG) synthesis-related genes. Conversely, the overexpression of CIDEA leads to an increase in the content of TAG and fatty acid. The results of mechanistic studies indicated that the overexpression of CIDEA inhibits AMP-activated protein kinase (AMPK) activity, which enhances the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and consequently increases the TAG content. Furthermore, the overexpression of CIDEA promoted the nuclear translocation of sterol regulatory element-binding protein 1 (SREBP1). Therefore, a theoretical framework is provided by this study for the regulation of lipid metabolism in dairy cows by means of nutrition and the hormone targeting of CIDEA.