FoxO1 Knockdown Promotes Fatty Acid Synthesis via Modulating SREBP1 Activities in the Dairy Goat Mammary Epithelial Cells.

Abstract

FoxO1 is a crucial transcription factor involved in lipid metabolism in mouse liver through repressing a key regulator of lipogenesis, sterol regulatory element binding protein 1 (SREBP1). However, it remains elusive whether FoxO1 plays roles in the regulation of fatty acid metabolism during lactation in dairy goats. In this study, we aim to investigate the function of FoxO1 in goat mammary epithelial cells (GMECs). We found that the expression of FoxO1 is significantly upregulated during lactation compared with the dry period. FoxO1 knockdown enhanced the expression of genes related to de novo fatty acid synthesis (e.g., FASN, ELOVL6 and SCD1) and triacylglycerol (TAG) synthesis (e.g., DGAT2 and GPAM). Consistently, intracellular TAG was significantly increased in FoxO1 knockdown cells and reduced in FoxO1 overexpression cells. Immunofluorescence staining revealed that insulin suppresses FoxO1 transcription by promoting its nuclear export. Further, we found that FoxO1 inhibits insulin-induced SREBP1 promoter activities in GMECs. Moreover, FoxO1 suppresses SREBP1 transcription via the LXR response element (LXRE) and SREBP response element (SRE) located in the SREBP1 promoter. Our data reveal that FoxO1 plays critical roles in regulating the synthesis of the fatty acid and triacylglycerol (TAG) in GMECs.