Skin Metabolism of Linoleic Acid: Enzymatic Pathways and Roles in Skin Homeostasis

Linoleic acid (LA), the most abundant polyunsaturated fatty acid (PUFA) in human skin, plays a pivotal role in maintaining cutaneous homeostasis. Emerging evidence links dysregulation of LA and its metabolites to various skin disorders, including acne vulgaris, atopic dermatitis, and psoriasis vulgaris. While reviews exist on the physiological roles of LA in human health, a dedicated synthesis focusing on its enzymatic metabolism within the skin remains absent. Capitalising on the skin's distinctive structural and enzymatic features, this review aims to synthesise current knowledge on linoleic acid metabolism while illuminating novel insights that reveal the previously underappreciated complexity of cutaneous LA‐mediated lipid signalling networks. (i) Linoleic acid undergoes three primary metabolic transformations in skin tissue: (a) serving as a substrate for β‐oxidation, (b) participating in lipid biosynthesis and conversion, and (c) undergoing enzymatic non‐catabolic oxidation to form bioactive lipid mediators. (ii) In the epidermis, LA primarily influences keratinocyte function through lipid biosynthesis and enzymatic oxidation pathways. In the dermis, LA predominantly affects sebaceous gland cells via β‐oxidation and lipid biosynthesis/conversion pathways. (iii) Further studies could concentrate on (a) the crosstalk between competing non‐catabolic oxidative routes (Lipoxygenases/Cytochrome P450 enzymes/Cyclooxygenases); (b) the paradoxical regulatory mechanisms controlling Lipoxygenases activation/inactivation; (c) the possible existence of linoleic acid/arachidonic acid (AA) intermediate in non‐sebaceous cells; (d) the divergent biological roles of LA versus AA in sebocyte regulation; and (e) the emerging evidence of oxidative stress as a positive modulator of sebum production.