The Omega 3 (n3) fatty acids abundant in fish oil have recently been identified as the components in the diet of fish eating populations which account for their enhanced cardiovascular health. Epidemiologic studies also point to a decreased incidence of skin disease (psoriasis) in fish eating populations, but the agents responsible and the mechanism involved in this alteration in the incidence of skin diseases are not known. This proposal sets forth the hypothesis that specific n3 fatty acids found in fish oil can regulate and alter normal epidermal biology. Since other fatty acids of the n6 polyunsaturated family and their eicosanoid derivatives are known regulators of epidermal biology, it is reasonable to propose that the n3 fatty acid family may alter the normal progression of keratinocyte differentiation by substitution for n6 fatty acids in membrane lipids, metabolic reactions, and structural components of the keratinocyte. We plan to enrich cultured human neonatal keratinocytes with either eicosapentaenoic (20:5n3) or docsahexaenoic (22:6n3) acids and monitor their proliferation and differentiation patterns, using known morphologic and biochemical markers of keratinocyte maturation. We will examine the pattern of incorporation of these fatty acids into cellular lipids as well as their metabolic products. Additionally, we will determine whether the n3 fatty acids are preferentially sequested into specific keratinocyte organelles. These studies should not only clarify what effect fish oil derived n3 fatty acids, now gaining popularity as dietary supplements, have on skin structure and function, but should also help to elucidate the mechanism by which these fatty acids alter epidermal biology.