牦牛主要分布于青藏高原，我国牦牛约占世界牦牛总量的92%，冷季饥饿是牦牛掉膘、死亡的首要因素。体脂动员是牦牛应对饥饿胁迫的主要方式，脂联素是动物应对饥饿胁迫和调节脂肪代谢的重要脂肪因子。β-羟基丁酸是饥饿动物主要的酮体，作为能源物质和前体参与机体代谢。近年小鼠研究表明β-羟基丁酸可作为信号分子与GPR109A受体结合调控脂联素表达。本课题组研究发现β-羟基丁酸可影响饥饿牦牛糖异生和脂联素表达，但调控机制不清楚。因此，本项目假设β-羟基丁酸可作为信号分子与GPR109A受体结合，使受体Gα和Gβγ亚基磷酸化，激活下游信号通路，调控饥饿牦牛脂联素表达。项目拟建立牦牛饥饿模型和脂肪细胞原代培养，通过对GPR109A受体过表达和抑制、对信号通路阻断和激活，揭示β-羟基丁酸作为信号分子调控饥饿牦牛脂肪细胞脂联素的信号通路，探明调控脂联素表达的新靶点，丰富牦牛脂肪代谢调控理论，促进牦牛科学饲养。

Yak is mainly distributed in the Qinghai-Tibetan Plateau, approximately 92% of the world's total yak population live in China. The primary factor responsible for body weight loss and death in cold season is starvation. Body fat mobilization is the main way for yak to deal with starvation stress, and adiponectin is an important adipocytokines for animals to cope with starvation stress and fat metabolism regulation. β-hydroxybutyric acid is the main ketone body of hungry animals, participating in body metabolism as energy substances and precursors. Recently, it was reported that β-hydroxybutyric acid acted as a signal molecule to bind with GPR109A receptor to regulate adiponectin expression in mice. Our team found that β-hydroxybutyric acid could affect adiponectin expression and gluconeogenesis in fasted yak, but the regulation mechanism was still unclear. Therefore, we hypothesize that β-hydroxybutyric acid can act as a signal molecule to bind with the GPR109A receptor, phosphorylate the receptor Gα and Gβγ subunits, activate downstream signal pathways, and finally regulate adiponectin expression in fasted yaks. In this project, the primary culture of adipocytes and yak starvation model will be established, and through overexpression and inhibition of GPR109A receptor, blocking and activating the signal pathways, in the aim of revealing the signal pathways of β-hydroxybutyric acid acting as a signal molecule to manipulate adiponectin expression in fasted yak adipocytes, exploring new targets to regulate adiponectin expression, perfecting regulation theory of yak fat metabolism, promoting the yak’s scientific breeding.