Circadian Gene <i>PER2</i> Silencing Downregulates <i>PPARG</i> and <i>SREBF1</i> and Suppresses Lipid Synthesis in Bovine Mammary Epithelial Cells

<i>PER2,</i> a circadian clock gene, is associated with mammary gland development and lipid synthesis in rodents, partly via regulating peroxisome proliferator-activated receptor gamma (<i>PPARG</i>). Whether such a type of molecular link existed in bovines was unclear. We hypothesized that <i>PER2</i> was associated with lipid metabolism and regulated cell cycles and apoptosis in bovine mammary epithelial cells (BMECs). To test this hypothesis, BMECs isolated from three mid-lactation (average 110 d postpartum) cows were used. The transient transfection of small interfering RNA (siRNA) was used to inhibit <i>PER2</i> transcription in primary BMECs. The silencing of <i>PER2</i> led to lower concentrations of cellular lipid droplets and triacylglycerol along with the downregulation of lipogenic-related genes such as <i>ACACA</i>, <i>FASN</i>, <i>LPIN1,</i> and <i>SCD,</i> suggesting an overall inhibition of lipogenesis and desaturation. The downregulation of <i>PPARG</i> and <i>SREBF1</i> in response to <i>PER2</i> silencing underscored the importance of circadian clock signaling and the transcriptional regulation of lipogenesis. Although the proliferation of BMECs was not influenced by <i>PER2</i> silencing, the number of cells in the G2/GM phase was upregulated. <i>PER2</i> silencing did not affect cell apoptosis. Overall, the data provided evidence that <i>PER2</i> participated in the coordination of mammary lipid metabolism and was potentially a component of the control of lipid droplets and TAG synthesis in ruminant mammary cells. The present data suggested that such an effect could occur through direct effects on transcriptional regulators.