Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites

Abstract

In the skin epidermis, the metabolism of polyunsaturated fatty acids (PUFAs) is highly active. Dietary deficiency of linoleic acid (LA), the major 18-carbon n-6 PUFA in normal epidermis, results in a characteristic scaly skin disorder and excessive epidermal water loss. Because of the inability of normal skin epidermis to desaturate LA to gamma-linolenic acid, it is transformed by epidermal 15-lipoxygenase to mainly 13-hydroxyoctadecadienoic acid, which functionally exerts antiproliferative properties in the tissue. In contrast, compared with LA, arachidonic acid (AA) is a relatively minor 20-carbon n-6 PUFA in the skin and is metabolized via the cyclooxygenase pathway, predominantly to the prostaglandins E(2), F(2)(alpha), and D(2). AA is also metabolized via the 15-lipoxygenase pathway, predominantly to 15-hydroxyeicosatetraenoic acid. At low concentrations, the prostaglandins function to modulate normal skin physiologic processes, whereas at high concentrations they induce inflammatory processes. PUFAs derived from other dietary oils are also transformed mainly into monohydroxy fatty acids. For instance, epidermal 15-lipoxygenase transforms dihomo-gamma-linolenic acid (20:3n-6) to 15-hydroxyeicosatrienoic acid, eicosapentaenoic acid (20:5n-3) to 15-hydroxyeicosapentaenoic acid, and docosahexaenoic acid (22:6n-3) to 17-hydroxydocosahexaenoic acid, respectively. These monohydroxy acids exhibit antiinflammatory properties in vitro. Thus, supplementation of diets with appropriate purified vegetable oils, fish oil, or both may generate local cutaneous antiinflammatory and antiproliferative metabolites which could serve as less toxic in vivo monotherapies or as adjuncts to standard therapeutic regimens for the management of inflammatory skin disorders.

Mass Spectrometric Studies on Epigenetic Interaction Networks in Cell Differentiation

“…Expression of PKC␤ is associated with proliferation of cells that retain the capability to undergo further differentiation, as evidenced by overexpression of PKC␤ in rat fibroblasts that decreased their sensitivity to growth inhibitory signals and increased their susceptibility to oncogenic transformation (52). PKC␤ has also been implicated in epidermal hyperproliferation induced by deficiency in essential fatty acid (53). This is consistent with our observations because we noted that when U937 cells were treated with PMA to stop proliferation and induce differentiation, the fatty acid synthetic and metabolic pathways were up-regulated, whereas the expression of PKC␤ was significantly reduced.…”

Diet Induced Modifications of Fatty-Acid Composition in Mealworm Larvae (Tenebrio molitor)

“…PUFAs influence cellular membrane fluidity, functions, signaling and expression (Jump, 2002). They play essential roles in brain functioning (Bradbury, 2011;Uauy, Hoffman, Peirano, Birch, & Birch, 2001), whole body metabolism (Arnold, Giroud, Valencak, & Ruf, 2015;Geiser & Kenagy, 1987;Hulbert, 2010;McGuire, Fenton, & Guglielmo, 2013;Munro & Thomas, 2004), muscular performance (Valencak, Arnold, Tataruch, & Ruf, 2003), immunity (Stanley & Miller, 2006;Stanley-Samuelson et al, 1991;Ziboh, Miller, & Cho, 2000) and reproduction (Fair, Doyle, Diskin, Hennessy, & Kenny, 2014;Rahman, Gasparini, Turchini, & Evans, 2014;Safarinejad, Hosseini, Dadkhah, & Asgari, 2010;Strzeżek, Fraser, Kuklińska, Dziekońska, & Lecewicz, 2004;Zalata, Christophe, Depuydt, Schoonjans, & Comhaire, 1998). Animal species use a combination of desaturases and elongases to convert alpha-linolenic acid (ALA, 18:3ω-3) and linoleic acid (LA,) into longer polyunsaturated chains.…”

Dietary Supplementation of Gamma-Linolenic Acid Improves Skin Parameters in Subjects with Dry Skin and Mild Atopic Dermatitis

“…The epidermal barrier is composed of intercellular lipid lamellae with ceramides, cholesterol and fatty acids in the stratum corneum. Any barrier disruption increases transepidermal water loss TEWL and epidermal hyperproliferation, both of which are observed in abnormal skin conditions such as essential fatty acid defi ciency 1,2 .…”

“…Prostaglandin E 1 PGE 1 and 15-hydroxyeicosatrienoic acid 15-HETrE converted from GLA via di-homo-gamma linolenic acid DGLA: 20:3n-6 has anti-infl ammatory properties. On the other hand, arachidonic acid AA: 20:4n-6 is a precursor of prostaglandins PG of the 2-series such as PGE 2 and leukotriene LT B 4 which exert hyper-proliferative and infl ammatory actions 7 . 15-HETrE is a potent inhibitor of LTB 4 generation and improves skin barrier function 8 10 .…”