肠道菌群失调调控丁酸/gga-miR-204/ACSS2轴促进鸡肝脏脂肪生成的分子机制研究

阐明脂肪生成分子机制对于肉鸡脂肪性状的遗传改良至关重要。最新研究显示肠道菌群与宿主脂肪生成密切相关。课题组前期研究发现肠道菌群失调促进鸡肝脏脂肪生成，机制分析提示肠道菌群失调可能降低肝脏丁酸丰度，下调gga-miR-204表达，上调其靶基因ACSS2表达促进肝脏脂肪生成。本项目拟通过丁酸钠饲喂和体外添加实验证明丁酸介导肠道菌群失调对肝脏脂肪生成的调控，明确丁酸调控gga-miR-204/ACSS2表达影响鸡肝脏脂肪生成的功能，利用敲低、过表达、双荧光素酶、RNA免疫沉淀和梯度转染实验证明gga-miR-204通过靶向调控ACSS2影响鸡肝脏脂肪生成，最终利用体外丁酸“拯救”和菌群移植实验阐明肠道菌群失调通过丁酸/gga-miR-204/ACSS2轴调控鸡肝脏脂肪生成的分子机制。本项目将有助于丰富鸡脂肪生成的调控理论，为鸡脂肪性状分子育种技术的建立提供理论依据。

Elucidating the molecular mechanism of lipogenesis is essential for the genetic improvement of fat traits in broilers. The latest researches show that gut microbiota is closely related to host lipogenesis. Our previous work found that gut microbiota dysbiosis promotes lipogenesis in chicken liver. The mechanism analysis suggests that gut microbiota dysbiosis may reduce the abundance of butyric acid in the liver. Decreased butyric acid abundance down-regulates liver gga-miR-204 expression and up-regulates gga-miR-204 target gene ACSS2 expression, and thereby promotes liver lipogenesis. This project intends to prove that the regulation of gut microbiota dysbiosis on liver lipogenesis is mediated by its metabolite butyric acid and the butyric acid affects liver lipogenesis by regulating the expression of gga-miR-204 and ACSS2 through feeding and in vitro addition experiments of sodium butyrate, to prove that gga-miR-204 affects liver lipogenesis by targeting ACSS2 using knockdown, overexpression, dual-luciferase, RIP and gradient transfection experiments. Finally, we hope to clarify the molecular mechanism of gut microbiota dysbiosis regulating chicken liver adipogenesis through the butyric acid/gga-miR-204/ACSS2 axis by in vitro butyric acid “rescue” and cecal microbiota transplantation experiments. This project will enrich the regulation theory of chicken lipogenesis and provide a theoretical basis for the establishment of molecular breeding technology for chicken fat traits.