Dietary effects on oxylipins

饮食对氧脂质的影响

• 批准号: RGPIN-2020-06215
• 负责人: Aukema, Harold
• 金额: $ 4.01万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717661
• 关键词: Dietary; effects; oxylipins

In our research program my HQP and I examine the effects of diet on bioactive fatty acid (FA) metabolites called oxylipins. These mediators are hormone-like lipids that signal many cellular processes. New advances in mass spectrometry are enabling the examination of oxylipins in a more comprehensive manner, allowing us learn more about FA functions. The long-term goal of our program is to determine how diet and sex affect these oxylipins, and to use these findings to extend our understanding of FA metabolism. We have shown that oxylipin levels are different in male and female rat tissues, and that these differences are influenced by dietary FA. Therefore, our first goal is to examine how diet and sex affect the activity of an enzyme (phospholipase A2) that we hypothesize is important in regulating these differences. We will use normal and gonadectomized rats provided different dietary oils. Sex differences are not the same in all tissues, so tissues that show a range of sex differences will be examined. We also will use cell culture so that we can examine how specific FA and sex hormones affect this protein. Little is known about sex differences in oxylipins, and even less is known about the effects of diet on these sex differences. We also have found that even though oxylipins mostly reflect the FA that they are made from, this is not always true. This gives us a new way of looking at FA metabolism. In our second goal we will examine how much of the essential omega-3 FA, alpha-linolenic acid (ALA), is needed in the diet by looking at oxylipins. In the past, the amount of dietary ALA required was determined by how much ALA is made into docosahexaenoic acid (DHA) in the body. We will provide rats different amounts of dietary ALA to determine how much the body makes not only of DHA, but also of the oxylipins made from DHA. Using both of these end points will add to the knowledge of dietary ALA requirements. For our third goal we will continue our research on the role of oxylipins in response to a possible toxin (a chloropropanol, CP) that is found in some foods. The study of oxylipins in toxicological studies is new and we showed that a CP changed the oxylipins in some tissues. We also think that the ALA in the diet may affect the toxic effects. Therefore, we will examine the oxylipins that are made in response to this CP in more tissues and with different levels of dietary ALA. This will tell us whether oxylipins may be a biomarker for toxic effects or whether the standard diet has adequate ALA. Examining oxylipins in this very controlled study also will provide a unique opportunity to investigate potential oxylipin functions. This research will help us understand more about sex differences in oxylipins and about the dietary requirement for ALA. It also will help us understand more about a toxin found in some foods and the role of oxylipins in its effects. Overall, this knowledge will add to our understanding of FA metabolism in the body.

在我们的研究项目中，我和我的HQP检查了饮食对生物活性脂肪酸（FA）代谢物（称为氧脂素）的影响。这些介质是类脂质，其向许多细胞过程发出信号。质谱分析的新进展使我们能够以更全面的方式检查氧脂素，使我们能够更多地了解FA的功能。我们计划的长期目标是确定饮食和性别如何影响这些氧脂素，并利用这些发现来扩展我们对FA代谢的理解。 我们已经表明，氧化脂质水平是不同的雄性和雌性大鼠组织，这些差异的影响，饮食FA。因此，我们的第一个目标是研究饮食和性别如何影响一种酶（磷脂酶A2）的活性，我们假设这种酶在调节这些差异方面很重要。我们将使用正常和性腺切除大鼠提供不同的饮食油。所有组织中的性别差异并不相同，因此将检查显示一系列性别差异的组织。我们还将使用细胞培养，以便我们可以检查特定的FA和性激素如何影响这种蛋白质。关于氧脂素的性别差异知之甚少，关于饮食对这些性别差异的影响更是知之甚少。 我们还发现，尽管氧脂素主要反映了它们的FA，但这并不总是正确的。这为我们提供了一种新的方式来看待FA代谢。在我们的第二个目标中，我们将通过观察氧化脂质来研究饮食中需要多少必需的omega-3 FA，α-亚麻酸（ALA）。过去，饮食中所需的ALA量取决于体内有多少ALA被转化为二十二碳六烯酸（DHA）。我们将为大鼠提供不同数量的膳食ALA，以确定身体不仅能产生多少DHA，还能产生多少由DHA制成的氧脂。使用这两个终点将增加饮食ALA需求的知识。 对于我们的第三个目标，我们将继续研究氧脂素在应对某些食物中发现的可能毒素（氯丙醇，CP）中的作用。氧化脂质在毒理学研究中的研究是新的，我们发现CP改变了某些组织中的氧化脂质。我们还认为饮食中的ALA可能会影响毒性作用。因此，我们将研究在更多组织中和不同水平的膳食ALA中对这种CP做出反应的氧脂素。这将告诉我们氧脂素是否可能是毒性作用的生物标志物，或者标准饮食是否含有足够的ALA。在这项非常受控的研究中检查氧脂素也将提供一个独特的机会来研究潜在的氧脂素功能。 这项研究将有助于我们了解更多关于氧化脂质的性别差异和ALA的饮食需求。它还将帮助我们更多地了解在某些食物中发现的毒素以及氧脂素在其作用中的作用。总的来说，这些知识将增加我们对体内FA代谢的理解。