Grant: Discovery Grants Program - Individual

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.