PCYT2 Inhibits Lipid Accumulation via the Notch Signaling Pathway in Chicken Primary Hepatocytes

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ABSTRACT Phosphatidylethanolamine cytidylytransferase 2 (PCYT2) is a key enzyme for phosphatidylethanolamine synthesis and plays a critical role in lipid metabolism. Our prior study revealed that PCYT2 exhibited differential expression in chicken liver between embryonic day 14 and post-hatch day 1 . However, its function and regulatory mechanism in chicken lipid metabolism remains unclear. In this study, overexpression and knockdown assays were performed to explore the role of PCYT2 in lipid metabolism using chicken primary hepatocytes, and the regulatory mechanism was further analyzed by transcriptome sequencing. The results showed that overexpression of PCYT2 significantly reduced lipid droplet content, triglyceride and total cholesterol levels in chicken primary hepatocytes. These reductions were associated with the downregulation of lipogenic-related genes and proteins (ACC and FASN) and the upregulation of fatty acid oxidation-related genes and proteins (CPT1, ACOX1, and ACSL1). Conversely, knockdown of PCYT2 produced opposite regulatory effects. Subsequently, transcriptome sequencing results demonstrated that overexpression of PCYT2 markedly suppressed the activity of the Notch signaling pathway. Activation of the Notch signaling pathway using Jagged-1 significantly attenuated the regulatory effects of PCYT2 overexpression on lipid metabolism in chicken primary hepatocytes. Specifically, Notch activation increased lipid content, upregulated the expression level of ACC and FASN, and downregulated the expression level of CPT1, ACOX1, and ACSL1 in PCYT2 -overexpressing hepatocytes. In summary, these results demonstrated that PCYT2 negatively regulates lipid accumulation in chicken primary hepatocytes by enhancing fatty acid oxidation and inhibiting lipogenesis, and the Notch signaling pathway is a critical mediator of this process. This findings provide a novel molecular target to improve hepatic lipid homeostasis and reduce fat deposition in chickens.

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