NUTRITIONAL SIGNIFICANCE OF POLYUNSATURATED FATTY ACIDS
Principal Investigator: Vincent Ziboh
Abstract: Enthusiasm that certain dietary oils are capable of influencing eicosanoid biosynthesis and some clinical conditions, have prompted a variety of studies, notably, that the dietary intake of Fish oil (which contains polyunsaturates: EPA (20:5n3) and DCHA (22:6n3) may be of preventive value in coronary heart disease while Evening Primrose oil (which contains LA (18:2n6) and GLA (18:3n6)) can improve atopic eczema. A serious flaw in these studies is the lack of information on the biological effects of the constituent PUFAs contained in these oils. To delineate the functional role of each of these PUFAs we propose in Phase I studies to feed the control group of guinea pigs a basal diet containing 2% of olive oil (which contains a minimum amount of linoleic acid to prevent EFA deficiency) while the experimental groups will receive: the basal diet supplemented with either 2% safflower oil, 2% primrose oil or 2% fish oil (menhaden oil). Purified blood PMNs and keratomed epidermis from the various animal groups will be removed and assessed for: (i) incorporation of PUFAs into PMNs and epidermal phospholipids; (ii) Ca2+ ionophore (A23187) induced generation of cyclooxygenase and 5- lipoxygenase products of: AA, EPA, GLA, and DCHA. (iii) Agonist-induced metabolism of PMNs prelabeled with 14C-AA and (b) incubation of 14C-AA by epidermal homogenates prepared from various PUFA fed animals. These studies should reveal whether the uptake of the PUFA mixtures by PMNs and epidermis do modify the abilities of the tissue and cell to transform 14C-AA into the 14C-eicosanoids. Additionally, we will assess PMN functional responses by: (i) N-formylmethionyl-leucyl- phenylalanine (FMLP) and LTB4- induced shape changes; (ii) FMLP-induced secretion responses in cytochalasin B pre-treated cells and (iv) FMLP and PMA-induced superoxide production. In Phase II studies, control G. pigs will be fed basal diet as described above; while the experimental groups will be fed the basal diet supplemented with either 0.68 g EPA-ethyl ester (EPA-E), 0.4g DCHA-E and 0.24g GLA-E for 4 weeks. Similar experiments as described in Phase I will be carried out with epidermis and PMNs isolated from the animal groups. Taken together, these studies should provide information on the dietary role of each of the PUFA on 14C-AA metabolism by epidermis and PMNs as well as on PMNs function.
Funding Period: 1988-02-01 - 1991-01-31
more information: NIH RePORT