Integration and control of metabolism of boar taint compounds

公猪异味化合物代谢的整合和控制

• 批准号: 36486-2012
• 负责人: Squires, EliJames
• 金额: $ 1.97万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=568737
• 关键词: Integration; control; metabolism; boar; taint

This research is designed to obtain a more complete understanding of factors affecting the accumulation of odorous compounds, skatole and androstenone, which cause off-odours and off-flavors (boar taint) in pork produced from uncastrated male pigs. Male pigs are routinely castrated at an early age to prevent boar taint, but castration raises concerns about animal welfare, as well as decreases the productivity of pig production. The results of this research could be used to develop alternative methods to control boar taint so that castration can be eliminated. We will study the role of different porcine cytochrome P450 (CYP450s) enzymes in the metabolism and clearance of skatole, which is produced by the gut microflora from tryptophan. In some male pigs, the hepatic metabolism of skatole in compromised, so that high levels of skatole accumulate in fatty tissue, resulting in boar taint. Androstenone is produced by the testis near maturity and acts as a sex pheromone. It is converted to sulphoconjugates and glucuronides by phase II conjugation reactions in the liver and excreted in the bile. We have recently shown that levels of androstenone can be reduced by including non-nutritive binding agents such as activated carbon in the diet. These compounds likely prevent the reabsorption of androstenone from the digestive tract via the enterohepatic circulation, and we now plan to carry out detailed studies to confirm this. The nuclear receptors CAR, PXR and FXR regulate the expression of CYP450s as well as phase II enzymes and we plan to characterize their central role in the regulation of genes that are involved in the metabolism of androstenone and skatole. We have also found that these receptors have several splice variants, and some of these produce dramatic and specific dominant positive or dominant negative effects on the activity of the wild type receptor; we plan to investigate the molecular mechanisms behind these effects. This work will develop a better understanding of how to control the problem of boar taint, but the pig is not only a valuable food animal but is also recognized as an excellent model for toxicological and pharmacological studies of relevance to humans.

本研究旨在更全面地了解影响恶臭化合物（粪臭素和雄甾烯酮）积累的因素，这些化合物会导致未去势公猪生产的猪肉产生异味和异味（野猪味）。雄性猪通常在很小的时候就被阉割，以防止公猪感染，但阉割引起了人们对动物福利的担忧，同时也降低了养猪的生产力。本研究的结果可用于开发替代方法来控制公猪腐败，从而消除去势。我们将研究不同的猪细胞色素P450（CYP 450）酶在代谢和清除粪臭素，这是由肠道微生物从色氨酸产生的作用。在一些雄性猪中，粪臭素的肝脏代谢受到损害，因此高水平的粪臭素积累在脂肪组织中，导致公猪腐臭。雄甾烯酮是由接近成熟的睾丸产生的，并作为性信息素。在肝脏中通过II相结合反应转化为磺基结合物和葡萄糖醛酸苷，并经胆汁排泄。我们最近表明，雄烯酮的水平可以通过在饮食中加入非营养性结合剂如活性炭来降低。这些化合物可能会阻止雄烯酮通过肠肝循环从消化道的重吸收，我们现在计划进行详细的研究来证实这一点。核受体CAR、PXR和FXR调节CYP 450以及II相酶的表达，我们计划表征它们在调节参与雄烯酮和粪臭素代谢的基因中的中心作用。我们还发现，这些受体有几个剪接变体，其中一些产生显着的和特定的显性积极或显性消极的野生型受体的活性的影响，我们计划调查这些影响背后的分子机制。这项工作将更好地了解如何控制野猪的问题，但猪不仅是一种有价值的食用动物，而且也被认为是与人类相关的毒理学和药理学研究的极好模型。