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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741097
• 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研究了饮食对生物活性脂肪酸(FA)代谢物氧脂的影响。这些介质是荷尔蒙样脂类物质，可以传递许多细胞过程的信号。质谱学的新进展使氧化脂质的检测更加全面，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是如何影响这些氧脂的，并利用这些发现来扩大我们对FA代谢的理解。我们已经证明，在雄性和雌性大鼠的组织中，氧脂水平是不同的，并且这些差异受到膳食FA的影响。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。我们将用正常和去性腺的大鼠提供不同的食用油。性别差异在所有组织中并不相同，因此将对表现出一系列性别差异的组织进行检查。我们还将使用细胞培养，这样我们就可以检查特定的FA和性激素如何影响这种蛋白质。人们对氧化脂质的性别差异知之甚少，对饮食对这些性别差异的影响更是知之甚少。我们还发现，尽管氧磷脂主要反映制造它们的脂肪酸，但这并不总是正确的。这为我们研究FA代谢提供了一个新的视角。在我们的第二个目标中，我们将通过观察氧化脂质来检查饮食中需要多少必要的omega-3脂肪酸，即α-亚麻酸(ALA)。在过去，膳食中ALA的需求量是由体内ALA转化为二十二碳六烯酸(DHA)的数量决定的。我们将给大鼠提供不同量的膳食ALA，以确定身体不仅制造了多少DHA，而且还制造了多少由DHA制成的氧化脂质。使用这两个终点将增加对膳食ALA需求的了解。为了我们的第三个目标，我们将继续研究氧磷脂在一些食物中发现的一种可能的毒素(氯丙醇，CP)的反应中所起的作用。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丙氨酸可能会影响其毒性作用。因此，我们将在更多的组织和不同水平的饮食ALA中检查因这种CP而产生的氧化脂质。这将告诉我们氧脂是否可能是毒性作用的生物标记物，或者标准饮食是否有足够的ALA。在这项非常对照的研究中检测氧脂也将为研究潜在的氧脂功能提供一个独特的机会。这项研究将帮助我们更多地了解氧化脂的性别差异和ALA的饮食需求。它还将帮助我们更多地了解一些食物中发现的一种毒素，以及氧化脂质在其影响中的作用。总体而言，这些知识将增加我们对体内FA新陈代谢的了解。