Ghrelin调控家禽脂肪代谢的机制研究

Chicken ghrelin is mainly expressed in proventriculus. Ghrelin stimulates the release of growth hormone and glucocorticoid (GC) and plays an negative regulating effect of food intake. Our previous study indicated that ghrelin is expressed in adipose tissue as well and the circulating ghrelin concentrations were altered by insulin. The present study focuses on that if ghrelin is involved in lipid metabolism in chicken. The effect of ghrelin on lipid metabolism was investigated at different energy status. Meanwhile, the interaction in secretion between insulin and GC and ghrelin was studied. Thereafter, the regulating effect of ghrelin on lipogenesis, lipid storage, and fatty acid oxidation in liver, adipose tissue, and skeletal muscles were respectively investigated further. Nutritional models and hormone administration models were employed in animal experiments and cell cultures to study the effect of ghrelin on lipid metabolism. The functions of relevant signaling pathways are evaluated by the gene expression and protein phosphorylation of target signaling molecules at the activation or inhibition status, respectively. The relevant results will be helpful for the understanding of physiological role of ghrelin in lipid metabolism of chickens and provide fundamental basis for the regulation of energy and lipid metabolism in chicken.

Ghrelin主要由家禽腺胃分泌，促进生长激素及糖皮质激素释放，对采食量具有负向调控效应。申请人前期研究发现ghrelin分泌受胰岛素影响，并在家禽脂肪组织中表达。因此，本项目拟研究的科学问题是"ghrelin在家禽脂肪代谢调控中的作用与机制"。针对这一科学问题开展以下内容研究：（1）ghrelin与胰岛素及糖皮质激素在分泌调控上的互作效应；（2）ghrelin对肝脏脂肪合成的调控规律与机制；（3）ghrelin对脂肪组织的代谢调控规律与机制；（4）ghrelin对骨骼肌脂肪酸氧化利用的影响规律与机制。在研究中利用动物试验和细胞体外培养相结合的方法，建立营养模型和激素调控模型，确定对脂肪代谢的影响规律。利用激活剂/抑制剂分别激活或阻断相关信号途径，测定基因表达及蛋白磷酸化水平，确定调控通路。该研究可揭示ghrelin对家禽脂肪代谢调控作用与机制，为家禽能量与脂肪代谢调控提供理论依据。

家禽ghrelin主要由腺胃分泌，与哺乳动物相反ghrelin对采食量具有负向调控效应，其受体在脂肪组织中有表达。针对这一现象，本项目提出的科学问题是“ghrelin在家禽脂肪代谢调控中的作用与机制”。本项目设定的研究目标是：确立ghrelin与机体脂肪代谢的联系，探明ghrelin调控脂肪合成与氧化利用的途径，阐明ghrelin的生物学作用。围绕上述科学问题与研究目标，本项目研究了Ghrelin表达的时空规律，能量代谢状态与ghrelin表达的关系，能量状态对肝、脂肪和成肌细胞ghrelin/GHSR-1a表达影响规律，ghrelin对肉鸡能量代谢的影响规律，ghrelin对肝细胞、肌纤维和脂肪细胞能量代谢的调控效应。研究发现ghrelin是机体能量代谢类型的重要调控信号，与胰岛素、糖皮质激素共同构成了机体的能量代谢调控网络；ghrelin抑制了肝脏、骨骼肌和脂肪组织对葡萄糖的摄取，促进了对脂肪酸的摄取与利用，通过激活AMPK信号通路促进脂肪分解代谢，证明家禽ghrelin在家禽能量代谢中具有重要的调控作用。研究实现了预定的研究目标，丰富了家禽能量代谢调控理论，证明ghrelin是一个重要能量代谢调控靶点，对于科学配合家禽日粮、提高饲料转化效率、改善肉品质具有重要的指导意义。在国际学术刊物上发表标注SCI论文14篇。