胆汁酸代谢在饲喂频率调控猪脂质代谢中的作用及其机理研究

Reducing lipid deposition is an important pathway to improve feed efficiency in swine production. Our previous findings indicated that decreasing feeding frequency leads to a lower lipid deposition, without impacting growth performance in pigs. Recent evidence showed that the metabolism of bile acids, which plays important role in the regulation of lipid metabolism, was affected by feeding frequency. Therefore, it is possible that the metabolism of bile acids mediated the effects of feeding frequency on lipid deposition. In the present study, effects of feeding frequency on lipid metabolism and the composition of secondary bile acids will be determined to investigate which types of bile acids were significantly influenced by feeding frequency. In addition, the cell culture experiment will be used to determine the biological activity of the bile acids that are affected by feeding frequency in the regulation of lipid metabolism associated pathway (farnesoid X receptor-mediated). Finally, dietary supplementation of bile acids with the most biological activity will be performed to test whether the influence of feeding frequency on lipid metabolism can be achieved by the changes in bile acids metabolism. The findings of the current project can provide important insights for the establishment of nutritional strategy to regulate lipid metabolism, and provide new ideas and refer for the improvement in feed efficiency by decreasing lipid deposition.

减少脂肪沉积是养猪生产过程中提高饲料转化效率的重要手段。项目组前期研究发现，通过降低饲喂频率可在不影响生长性能的条件下减少脂肪沉积并提高饲料转化效率。近期研究表明，在脂质代谢过程中具有重要调控作用的胆汁酸代谢受饲喂频率的影响。由此推测，饲喂频率可能是通过调控胆汁酸代谢影响脂沉积。因此本项目首先通过研究饲喂频率对猪脂质代谢和次级胆汁酸组成的影响，筛选出受饲喂频率影响较大的胆汁酸类型；随后通过体外细胞培养实验比较受饲喂频率调控的胆汁酸类型在脂质代谢相关（法尼醇X受体介导）信号通路中的生物学活性差异，明确发挥作用的主要胆汁酸类型；最后通过饲粮添加筛选出的生物学活性最强的胆汁酸类型验证饲喂频率是通过调控胆汁酸代谢影响脂质代谢。本项目研究结果可为脂质代谢的营养调控方案提供参考，为通过减少脂肪沉积改善饲料报酬提供新的思路和途径。

在生猪养殖行业中，减少脂肪沉积和增加蛋白质合成是改善饲料报酬提高畜牧生产效率的重要手段。依靠自动化料线的自由采食模式虽然能够保证最大的日增重，但与此同时也增加了脂肪的沉积并在一定程度上降低了饲料报酬。鉴于胆汁酸代谢是影响猪脂质代谢的重要途径，本项目以此作为切入点研究了胆汁酸代谢在饲喂频率调控猪脂质代谢中的作用和机理。研究结果表明，在30-120千克阶段限制饲喂频率组的平均日采食量和平均日增重与自由采食组无显著差异，但饲料转化效率由2.84显著降低到2.58，脂肪沉积减少是饲料转化率降低的主要原因。质谱分析结果指出，限制饲喂频率显著增加了粪便中牛磺胆酸、猪去氧胆酸、牛磺猪去氧胆酸、牛磺鹅去氧胆酸、胆酸、鹅去氧胆酸、去氧胆酸等初级胆汁酸和次级胆汁酸的含量。与自由采食组相比，限制饲喂频率增加了肠道中Subdoligranulum, Roseburia, Mitsuokella和Terrisporobacter的丰度，降低了Spirochaetaceae, Methanobrevibacter, Bacteroidales, Alloprevotella, Parabacteroides和Bacteroides的水平。代谢组学分析表明，饲喂频率显著改变了血液中氨基酸代谢和脂质代谢相关代谢产物的含量。在此研究结果之上，通过在生长猪日粮中添加胆汁酸的试验表明，生长猪日粮全程添加胆汁酸可在不影响日采食量和日增重的情况下改善饲料报酬，但对脂肪沉积的关键指标背膘厚度无显著影响，说明提高脂肪消化率可能是改善饲料报酬的重要途径。此外，在肠道内环境和微生物的作用下，日粮添加胆汁酸对猪血清和粪便中胆汁酸含量以及胆汁酸组成和微生物多样性均无显著影响。由此可见，胆汁酸代谢途径仅是饲喂频率调控猪脂质代谢的途径之一，与饲喂频率相关的内分泌水平的改变可能在脂质代谢过程中也发挥着重要作用。综上所述，通过降低饲喂频率减少脂肪沉积达到改善饲料报酬和胴体品质的饲喂手段具有推广意义。