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Investigators | Department | Objectives | Approach Keywords | Progress Reports | Impact Statements | Publications | |
Project * COL00289B(See Project History for COL00289A) | |
| Title | N-3 Polyunsaturated Fatty Acids and Human Health and Disease |
| Investigator(s) | Allen, KG; Anderson, JE; |
| Department | Food Science and Human Nutrition |
| Objectives | 1. To determine the health promotion and disease prevention effects of both the forms and the amounts of n-3 fatty acids by correlation with tissue functions, and with alterations in biomarkers, relevant to optimal health and disease prevention. 2. To examine dietary levels of both form and amount of n-3 polyunsaturated fatty acids (PUFA) that promote health and reduce disease that are relevant and achievable in human diets using the human equivalent dose method (allometric scaling) in rodent models. 3. To develop, test and disseminate effective means for translating research on the health promoting and disease preventing effects of n-3 PUFA into consumer food choices. |
| Approach | Randomized clinical trials (RCT) are expensive approaches to defining the effects of nutrients on disease outcomes and often use supplementary levels that are unachievable in human diets. We have addressed this problem in rodent models by validating the human equivalent dose (HED) allometric scaling approach to rodent experiments with n-3 PUFA. We now propose to extend this to cell culture (in vitro) models, validate this approach, and develop a high-throughput preclinical screening tool that will contribute to defining the forms and amounts of n-3 PUFA in health promotion and disease prevention. Our preliminary data shows that incorporation of DHA into membranes of PHM1-41 cells decreases oxytocin (OT)-mediated Ca2+ entry. Decreased Ca2+ in myometrial cells could be one mechanism by which long-chain n-3 PUFA increases gestational duration. We propose to investigate this mechanism and to compare ALA, LA, EPA and DHA. In all cases our control is oleic acid (OA) since is an abundant fatty acid in the membranes (preliminary data). Fatty acids, provided bound to bovine serum albumin (BSA), will be provided at 10 μM, 30μM and 100μ ;M concentrations. We will examine the following aspects of the OT signaling pathway: Membrane fatty acid composition; Intracellular Ca2+ concentrations in response to OT binding; inositoltrisphosphate (IP3) concentrations as a result of OT binding to the OT receptor; OT receptor number in membrane preparations. Translation of the scientific findings to consumers and nutritional professionals (Extension educators, dieticians, nutritionists) will be accomplished using an accessible web-based venue such as eXtension. Colorado station will investigate the human equivalent dietary doses of preformed long-chain n-3PUFA (eicosapentaenoic, EPA, and docosahexaenoic acids, DHA) that will improve reproductive tissue prostaglandin (PG) and matrix metalloproteinase (MMP) indices of premature delivery. We will also determine if these dietary n-3 fatty acid sources will be more effective than α-linolenic acid (ALA), even when fed at supplementary intakes, in improving these outcomes and promoting health. We will also examine the effect of human equivalent doses of arachidonic acid (AA)in altering the responsiveness to DHA and EPA. We will also examine the influence of long-chain n-3 PUFA incorporation (EPA, DHA) into membranes of cultured human late-pregnancy myometrial cells on oxytocin-mediated Ca2+ entry via decreased inositol trisphoshate signaling and decreased membrane oxytocin receptor density or ligand binding. The ability of both linoleic acid (LA) or ALA incorporation into membranes of these human myometrial cells to alter Ca2+ dynamics will also be examined. |
| Keywords | n-3 polyunsaturated fatty acids, docosahexaenoic acid, eicosapentaenoic acid, linoleic acid, linolenic acid, arachidonic acid, diet, requirements, premature delivery, gestational duration; |
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