PPARγ-LXRα信号通路介导桑叶黄酮调控巴马香猪脂质代谢的作用机制研究

Dyslipidemia is a key risk factor that threatens the health of human beings. Pork has been our main meat, and much fat intake can lead to the occurrence of obesity and cardiovascular disease. Therefore, how to reduce fat deposition to improve animal products has become one of the key solutions to the problem of food security in the present. As medicine and edible plant, the flavonoids compound of mulberry leaves (FML) show a notable effect on decreasing hematic lipid, lowering blood pressure, inhibiting the formation of atherosclerosis, and other biological activity. The applicant has been engaged in the research of meat quality characteristics and its nutritional regulation measures in local pig for many years, and has made good progress. The previous studies in our research group showed that diets added mulberry leaves could decrease blood lipid concentrations in finishing pigs. But the regulation of FML on lipid metabolism of pigs and its mechanism are unclear. The PPARγ-LXRα signal pathway is one of the important ways to participate in the regulation of lipid metabolism. Therefore, the purpose of this study intends to, through animal experiment and in vitro cell culture test, investigate the effect of FML on lipid synthesis, transport, metabolism and degradation in Bama mini-pig and adipocyte model, and the regulation mechanism of FML on PPARγ-LXRα signaling pathway and its downstream molecules expression. The research result will reveal the effect and regulation mechanism of FML on lipid traits and lipid metabolism in pigs, which will provide a theoretical basis for FML as functional feed additive, and will enrich and improve the exploitation and utilization of mulberry leaves in animal husbandry.

血脂异常已成为威胁我国人民健康的重要危险因素。猪肉是我国主要肉类食品，而过多的动物脂肪摄入会导致人肥胖症和多种心血管疾病的发生，因此减少动物产品中的脂肪沉积已成为解决食品安全问题的主要途径。桑叶作为药食同源植物，其主要活性成分黄酮类化合物（FML）具有很强的降血脂、降血压及抑制动脉粥样硬化等功效。申请人多年来从事地方猪肉质特性与营养调控研究，并取得较好进展；前期研究发现，桑叶粉可降低肥育猪的血脂浓度，但对FML调控猪脂质代谢的分子机制尚不清楚。因此，本项目拟通过动物饲养和体外细胞培养试验，研究FML对巴马香猪脂质合成、转运和分解代谢的影响，探讨其对脂肪细胞PPARγ-LXRα信号通路（参与脂质代谢调控的重要信号途径）及其下游分子的调控作用，初步揭示FML对生长猪脂肪性状和脂质代谢的调控机理，为FML作为功能性饲料添加剂提供理论依据，更能丰富和完善桑叶在畜牧业中的开发与利用。

血脂异常已成为威胁我国人民健康的重要危险因素。猪肉是我国主要肉类食品，而过多的动物脂肪摄入会导致人肥胖症和多种心血管疾病的发生，因此减少动物产品中的脂肪沉积、改善产品品质已成为解决食品安全问题的主要途径。桑叶作为药食同源植物，其主要活性成分黄酮类化合物（FML）具有很强的降血脂、降血压及抑制动脉粥样硬化等功效。前期研究发现，桑叶粉可降低肥育猪的血脂浓度，但对FML调控猪脂质代谢的分子机制尚不清楚。因此，本项目结合动物饲养和体外细胞培养试验，通过日粮添加不同剂量的FML，研究其对巴马香猪生长性能、胴体性状、肉品质、血液生化参数和抗氧化指标、肌肉组织形态学特性、不同组织的化学组成和PPARγ信号通路以及下游分子LXRα及ABCA1的mRNA表达量和蛋白质丰度的影响；同时利用3T3-L1前脂肪细胞模型，采用PPARγ激动剂或抑制剂处理后，研究FML对3T3-L1前脂肪细胞增殖、分化等影响。结果表明，桑叶黄酮提高巴马香猪的末重、日增重和胴体长，降低料重比、体脂率、滴水损失和剪切力值，从而改善其生产性能；降低试验猪的HMGCR活性、TC、TG和游离脂肪酸含量，增强了LPL和ATGL酶活；添加组猪血清中的SOD和CAT酶活显著增加，MDA含量显著降低，有利于增强机体抗氧化能力；提高试验猪不同组织部位中n-3PUFA含量，降低∑n-6/∑n-3比值，改善机体脂质代谢；添加FML提高试验猪机体ABCA1和PPARγ基因表达水平和蛋白丰度，在肌肉和脂肪组织中尤为明显，发挥降脂效应。本项目以与人生理及解剖结构相似的猪为研究载体，探讨FML对猪脂质合成与吸收、转运与代谢的调控作用，阐明其发挥糖脂调控作用的关键作用因子和信号途径，为降低动物脂肪沉积、生产优质畜禽产品、增强健康生态养殖提供营养调控/干预手段，对畜牧业可持续发展具有重要理论和实践意义；同时为研究人类糖脂代谢，防治高血脂症提供理论参考。