GPR41介导乙酸调控围产后期奶牛脂肪代谢的分子机制

高产奶牛在围产后期会发生异常的脂肪动员，生成过量的NEFA以及脂肪合成减少，造成能量代谢失衡，从而诱发代谢紊乱。反刍动物不能利用葡萄糖合成脂肪，而是利用乙酸作为主要前体物从头合成脂肪。GPR41是乙酸的特异性受体。乙酰辅酶A羧化酶α（ACCα）和激素敏感脂肪酶（HSL）磷酸化修饰对能量平衡发挥至关重要的作用。本项目假设乙酸激活GPR41抑制ACCα和HSL的磷酸化，促进脂肪合成，减少NEFA释放，调节围产后期奶牛能量平衡。拟应用转录组学和AAV9-CRISPR/Cas9体内敲除相结合技术，研究GPR41介导乙酸调控围产后期奶牛GPR41-cAMP-PKA-ACCα/HSL轴信号通路蛋白表达机制，揭示GPR41介导乙酸调控围产后期奶牛脂肪代谢的分子机制。本项目预期在围产后期奶牛脂肪代谢调控基础理论方面取得新突破，并对整个泌乳期产奶性能的提高具有重要指导意义。

Dysregulated lipid mobilization results in a massive release of NEFA and a decrease in lipogenesis, triggering the energy imbalance and metabolic disorders in postpartum high yield dairy cattle. The glucose cannot be converted into fat in ruminant, but acetate was considered the principal generator for de novo fat synthesis. GPR41 is as specific receptor for acetate. The phosphorylation modification of acetyl CoA carboxylase alpha (ACCα) and hormone sensitive lipase (HSL) play a vital role in the energy balance. The project hypothesized that acetate activates the GPR41 to inhibit the phosphorylation of ACCα and HSL, contributing to the lipogenesis and a decrease in release of NEFA, and regulates the energy balance in postpartum dairy cattle. The project will carry out the transcriptomics and adeno-associated virus 9 (AAV9)-CRISPR/Cas9 knockout in vivo technology to study the mechanism of GPR41-mediated the acetate regulating the protein expression involved in GPR41-cAMP-PKA-ACCα/HSL signal pathway axis in postpartum dairy cattle, and to reveal the molecular mechanism of GPR41-mediated the acetate regulating the fat metabolism in postpartum dairy cattle. The finding of this project will be expected to obtain new breakthrough in the understanding of the basic theory for regulating the fat metabolism in postpartum dairy cattle, and has an important guiding significance in improving milk performance in the whole lactation period.