Lipidome Complexity in Physiological and Pathological Skin Pigmentation

Abstract

Skin pigmentation results from complex cellular interactions and is influenced by genetic, environmental, and metabolic factors. Emerging evidence highlights the multiple pathways by which lipids regulate melanogenesis and points to lipid metabolism and signaling as key players in this process. Lipidomics is a high-throughput omics approach that enables detailed characterization of lipid profiles, thus representing a valid tool for evaluating skin lipid functional role in both physiological melanogenesis and pigmentary disorders. The use of lipidomics to gain a deeper comprehension of the role of lipids in skin pigmentation is still an evolving field, but it has allowed the identification of significant lipid dysregulation in several pigmentary pathologies. This review summarizes the current knowledge on the involvement of lipids in skin pigmentation, focusing on lipid profile alterations described in hyper- and hypopigmentary disorders such as post-inflammatory hyperpigmentation, melasma, solar lentigo, and vitiligo. Lipidomic profiling reveals disease-specific alterations supporting the pivotal role of lipid signaling in the physiopathological mechanisms of melanogenesis. These findings provide insights into disease pathogenesis and show promise for the discovery of biomarkers and innovative therapeutic strategies for pigmentary disorders.

Keywords: lipidomics; lipids; melanin; melanogenesis; melasma; skin; solar lentigo; vitiligo.

Figure 1

Schematic overview of lipid-related dysregulation occurring in hyperpigmentary disorders. CE: cornified envelope; CERs: ceramides; VLC: very long chain (VLC) Cers; ULC: ultra-long chain Cers; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PS: phosphatidylserine; FA: fatty acid; LTB4: leukotriene B4; LTC4: leukotriene C4; LTD4: leukotriene D4; LTE4: leukotriene E4; TXB2: thromboxane B2; 12-HETE: 12-hydroxy eicosatetraenoic acid; COX2: cyclooxygenase-2; PGE2: prostaglandin E2; PGF2a: prostaglandin F2a; PGD2: prostaglandin D2; PPARα: peroxisome proliferator-activated receptor α; PPARγ: peroxisome proliferator-activated receptor γ; SASP: senescence-associated secretory phenotype; AA: arachidonic acid; SG: sebaceous gland. The arrows in the Figure indicate the following: ↑ increased level of the indicated parameters; ↓ decreased level of the indicated parameters.

Figure 2

Schematic overview of lipid-related dysregulation highlighted in the cutaneous lipidome (A) and at systemic level (B) in vitiligo. FFAs: free fatty acids; CERs: ceramides; CH: cholesterol; CHS: cholesterol sulfate; VLC: very long chain; ULC: ultra long chain; CL: cardiolipin; HMG-CoA reductase: 3-Hydroxy-3-methylglutaryl coenzyme A reductase; ALA: alpha-linolenic acid; PAF: platelet-activating factor; ARA: arachidonic acid; FAs: fatty acids; TGs: triglycerides; LDL: low-density lipoprotein; HDL: high-density lipoprotein; 7KC: 7-ketocholesterol; 7-beta-HC: 7 beta-hydroxycholesterol; SG: sebaceous gland. The arrows in the Figure indicate the following: ↑ increased level of the indicated parameters; ↓ decreased level of the indicated parameters.