豆粕致虹鳟低胆固醇血症的关键因素及其调控机制

A large number of studies show that replacing fish meal with high levels of soybean meal may result in hypocholesterolemia in fish. However, cholesterol is an important and indispensable substance of animal tissue cells, which plays an important role in maintaining the physiological function of fish. Thus, the cholesterol-lowering action of soybean meal will restrict the utilization of soybean meal in fish feeds. Clarifying the key factors for hypocholesterolemia in fish induced by feeding high levels of soybean meal and its regulatory mechanism could provide a new idea or approach for improving the utilization efficiency of plant-derived protein sources (such as soybean meal) in fish feeds. Based on our previous studies, a series of experiments, using rainbow trout (Oncorhynchus mykiss) as a test fish and taking soybean meal as the representative of plant-derived protein sources, were designed to compare the effects of (1) cholesterol and related substances (such as taurine and glycine) in fish meal, (2) soy protein (i.e. soy protein isolate) versus fish protein (i.e. fish protein concentrate), (3) various soy products (such as soybean meal, soy protein concentrate, soy protein isolate, soy peptide), and (4) non-protein components of soybean meal (such as soy saponines and phytosterol) on the serum total cholesterol level of rainbow trout, thereby to distinguish the key factors for hypocholesterolemia in fish induced by feeding high levels of soybean meal (i.e. the decreased dietary supply of exogenous cholesterol due to the withdrawal of fish meal, the inhibition of endogenous cholesterol synthesis, or both?). In addition, the present study will also examine the effects of key factors for hypocholesterolemia on the regulation of cholesterol metabolic homeostasis (i.e. cholesterol digestion and absorption, biosynthesis, transform, and excretion) in rainbow trout. The ultimate objective of the present study is to distinguish the key factors for hypocholesterolemia in rainbow trout induced by feeding high levels of soybean meal and its regulatory mechanism. The results obtained in the course of the study are expected to have significant academic contributions and practical implications.

研究表明，豆粕高比例替代鱼粉可致鱼类低胆固醇血症。胆固醇是动物组织细胞所不可缺少的重要物质，对维持鱼体正常生理机能起着重要作用。因此，豆粕的降鱼类血胆固醇效应将限制其在鱼类饲料中的应用。阐明豆粕致鱼类低胆固醇血症的成因及机制可为如何提高鱼类对豆粕等植物蛋白源的利用提供一条新的思路和途径。本项目拟在前期研究基础上，以虹鳟作为鱼类代表，以豆粕作为植物蛋白源代表，比较研究①鱼粉中所含胆固醇及相关物质、②大豆蛋白与鱼粉蛋白、③不同大豆制品、④豆粕中主要非蛋白组分对虹鳟血液胆固醇水平的影响，以筛选豆粕替代鱼粉致虹鳟低胆固醇血症的关键因素(外源性胆固醇的供应不足？或是内源性胆固醇的合成受限？抑或是两者兼有？)；并着重分析关键因素对虹鳟胆固醇消化吸收、生物合成、转化和排泄等胆固醇代谢平衡调控的影响，进而阐明豆粕致虹鳟低胆固醇血症的关键因素及其调控机制，预期研究成果将具有重要的理论价值和广泛的应用前景。

研究表明，豆粕高比例替代鱼粉可致鱼类低胆固醇血症。胆固醇是动物组织细胞不可缺少的重要物质，对维持鱼体正常生理机能起着重要作用。因此，豆粕降鱼类血胆固醇效应将限制其在鱼类饲料中的应用。本项目以虹鳟作为鱼类代表，比较研究了①不同大豆制品(豆粕、大豆浓缩蛋白、大豆分离蛋白)；②豆粕中主要非蛋白组分(大豆皂甙、植物甾醇)；③鱼粉中所含胆固醇及相关物质(牛磺酸、甘氨酸)；④大豆蛋白与鱼粉蛋白差异(蛋白质结构差异[大豆分离蛋白VS大豆肽]、必需氨基酸[蛋氨酸、赖氨酸、精氨酸、亮氨酸]组成差异)等四个方面因素对虹鳟血清总胆固醇(TC)水平的影响，以筛选豆粕高比例替代鱼粉致虹鳟低胆固醇血症的关键因素(外源性胆固醇的供应不足？或是内源性胆固醇的合成受限？抑或是两者兼有？)；并着重分析了关键因素对虹鳟胆固醇吸收、合成、转化和排泄等胆固醇代谢平衡调控的影响。结果表明：豆粕高比例替代鱼粉所致虹鳟低胆固醇血症与豆粕中所含抗营养因子(主要为植物甾醇)和/或非淀粉多糖，鱼粉中所含胆固醇、牛磺酸和甘氨酸，大豆蛋白大分子结构密切相关；而与豆粕中所含大豆皂甙、大豆蛋白和鱼粉蛋白中必需氨基酸(蛋氨酸、赖氨酸、精氨酸、亮氨酸)组成差异无关。豆粕中所含抗营养因子和/或非淀粉多糖明显抑制虹鳟肠道内胆固醇吸收(肠道ACAT活性降低，而CEL活性升高)，并促进体内胆固醇转化(肝脏ACAT活性及其mRNA水平降低，而LCAT活性及其mRNA水平升高)和排泄(粪便胆固醇排出率升高)，从而降低血液TC水平；鱼粉中所含胆固醇、牛磺酸和甘氨酸协同调控胆汁酸代谢(肝脏CYP7A1活性及其mRNA水平升高)，抑制胆固醇转化，从而提高血液TC水平；大分子大豆蛋白抑制胆固醇合成(肝脏HMGCR活性及其mRNA水平降低)，从而降低血液TC水平。本项目为提高鱼类对豆粕的利用效率提供了一条新的解决思路和途径，具有重要的理论价值和广泛的应用前景。