维生素A/视黄酸通过VEGFA/VEGFR2信号通路调控肉羊肌内脂肪形成的机制

Intramuscular fat increases meat tenderness and juiciness. Increasing marbling score significantly raises the price of meat. We previously found that neonatal vitamin A injection promotes intramuscular adipogenesis and increases marbling score of beef cattle. In mice, one of the Vitamin A’s metabolites, retinoic acid （RA）, increases the population of preadipocytes in intramuscular fat by promoting angiogenesis and induces beige adipogenesis partly through vascular endothelial growth factor A （VEGFA）. The proposed study is aimed to explore whether and how Vitamin A and RA, regulates intramuscular preadipocytes differentiation through VEGFA/VEGFR2 signaling. We plan to isolate intramuscular preadipocyte from sheep and immortalize them to make a cell line. The cells will be cultured and induced adipogenesis in a 3D culture system that we previously developed. Both in vitro and in vivo study will be performed to study the regulatory effects of vitamin A/RA on the adipogenic differentiation of intramuscular adipocytes and the relationship between nutrients, circulation system and intramuscular fat. This study will provide a perfect model for intramuscular fat studies and data obtained will help improve meat quality.

肌内脂肪可以提高肉的嫩度和多汁性，同时增加肉的风味，改善肉品质从而提高肉的经济价值。我们前期研究发现初生期注射维生素A可以促进肉牛肌内脂肪细胞分化，提高大理石纹评分。此外，我们还发现维生素A 代谢产物视黄酸（retinoic acid, RA）通过调控血管内皮生长因子VEGFA来提高小鼠皮下脂肪中前脂肪细胞数目并诱导其分化。综合前期研究结果，本项目旨在探讨维生素A及RA通过VEGFA/VEGFR2信号通路来调控肌内前脂肪细胞分化的作用机制。本项目拟从绵羔羊肌肉中分离肌内前脂肪细胞建立细胞系，利用我们建立的三维体系培养、诱导肌内前脂肪细胞。同时结合动物实验，研究维生素A/RA对肌内脂肪中血管形成和前脂肪细胞分化的作用，并探讨营养、血管和肌内脂肪三者之间的关系。本项目将建立绵羊肌内脂肪体内和体外发育的研究模型，为肌内脂肪的研究提供工具，为大理石纹肉的生产提供理论依据。

肌内脂肪提高肉的嫩度和多汁性，增加肉的风味，改善肉品质，从而提高肉的经济价值。我们前期研究发现初生期注射维生素A可以促进肉牛肌内脂肪细胞分化，提高大理石纹评分。项目探究了初生期注射维生素A对肉羊肌内脂肪细胞分化与脂质沉积的作用及其机制。本项目发现，初生期注射维生素A通过VEGFA/VEGFR2信号通路促进了肌肉中血管发育，增加了肌内脂肪前体细胞数目并促进其分化能力，增加了肌内脂肪细胞的数目，提高了肌内脂肪的沉积能力。与对照组相比，维生素A处理组肉羊屠宰时背最长肌中肌内甘油三酯含量增加了82%。本项目建立了绵羊肌内前体脂肪细胞成脂分化的三维培养、诱导体系，能够对血管生成、脂肪前体细胞生成、脂肪细胞分化和脂肪沉积四个体内发育过程进行模拟。该项目的研究结果加深了我们对于反刍家畜肌内脂肪发育规律的理解，为肉羊早期饲养技术创新提供了理论基础，在高档羊肉生产方面有很好的应用前景。