The skin epidermis has some unique metabolic properties regarding the way it handles long chain polyunsaturated fatty acids (PUFA). Deficiency in certain PUFA can lead to inflammation of the epidermal cells and result in a number of skin disorders. Arachidonic acid (AA, 20:4 (n-6)) is the second most abundant PUFA in epidermal cells making up roughly 10% of the total fatty acid content of phospholipids in human epidermal cells. Arachidonic acid is released from the phospholipids membranes by the action of the cytosolic phospholipase A2. Following release, AA can then undergoes oxidation via the cyclooxygenase pathway to form series 2 prostaglandins (PGE2, PGF2α and PGD2), or alternatively via the lipoxygenase pathway to form the series 4 leukotrienes (LTA4, LTB4, LTC4, LTD4, LTE4). Both the series 2 prostaglandins and the series 4 leukotrienes are pro-inflammatory, however there is limited 5-lipoxygenase in epidermal cells and so conversion to the leukotrienes is limited.
The pro-inflammatory effects of AA can be decreased by the presence of other PUFA. Linoleic acid (LA, C18:2 (n-6)) is the most abundant PUFA in the skin, but epidermal cells lack the ∆6-desaturase enzyme and so cannot convert LA to γ-linolenic acid (GLA, 18:3 (n-6)). Instead LA is metabolised to 13-hydroxyoctadecadienoic acid, which performs an anti-proliferative function in skin. When levels of GLA are elevated in epidermal cells, metabolism to dihomo-γ-linolenic acid (DGLA, 20:3 (n-6)) increases. In skin cells DGLA is metabolised to series 1 prostaglandins (PGE1) by cyclooxygenase and also to 15-hydroxyeicosatrienoic acid (15-HETrE) by 15-lipoxygenase. Diets high in GLA, such as those containing evening primrose oil or borage oil, raise skin levels of GLA and this in turn raises levels of DGLA and its metabolites (PGE1 and 15-HETrE). This has a pronounced anti-inflammatory effect in skin cells. The ∆5-desaturase enzyme is missing from skin and so GLA is not converted to AA.
The essential fatty acid α-linolenic acid (ALA, C18:3 (n-3)) and its oxidative metabolites, the marine long chain fatty acids eicosapentanoic acid (EPA, C20:5 (n-3)) and docosahexanoic acid (DHA, C22:6 (n-3)) are not present in normal epidermis in large concentrations. However, EPA and DHA can be metabolised in skin cells to form 15-hydroxyeicosapentanoic acid (15-HEPE) and 17-hydroxydocosaheanoic acid (17-HoDHA), via the 15-lipoxygenase enzyme. Consumption of fish oils in high amounts is able to raise epidermal levels of 15-HEPE and 17-HoDHA which may explain the benefits of fish oils on skin conditions of inflammation. The conversion of ALA to EPA and DHA in humans is slow and it is therefore likely that consumption of dietary sources of ALA do not raise levels of EPA and DHA in skin cells to the same degree as EPA and DHA in the diet. It is therefore likely that ALA does not have such pronounced anti-inflammatory effects as the marine oils.
Possible metabolism of long chain polyunsaturated fatty acids in skin. GLA = gamma linolenic acid; DGLA = dihomo gamma linolenic acid; PG = prostaglandin; LT = leukotriene; HETrE = hydroxyeicosatrienoic acid; HETE = hydroxyeicosatetranoic acid; HODE = hydroxyoctadecadienoic acid
RdB
