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    • A mutation in stearoyl coenzyme A desaturase

    2022-01-21

    A mutation in stearoyl coenzyme A desaturase 1 gene was reported to reduce sebum production and monounsaturated fatty acids (MUFA) synthesis in mice, which was accompanied with impaired clearance of gram-positive bacteria-induced skin infection (Georgel et al., 2005). Interestingly, gram-positive bacteria initiate innate immune responses through toll-like receptor 2, which leads to the transcription of stearoyl coenzyme A desaturase 1 (Georgel et al., 2005). The majority of epidermal surface lipids is of sebaceous origin, which is released by the sebaceous glands and contains mainly non-polar lipids, including triglycerides, wax esters, squalene, fatty acids, and smaller amounts of cholesterol, cholesterol esters, and diglycerides (De Luca & Valacchi, 2010). Keratinocytes produce a small fraction of the epidermal surface lipids, which are a mixture of free fatty acids, cholesterol, and ceramides in almost equal amounts (Pappas, 2009). Glycerophospholipid, sphingolipid, and cholesterol form the backbone of plasma membrane and intracellular membranes, which only allow certain amount of specific molecules to traffic and transmit signals through a chain of molecular events (Holthuis & Levine, 2005). As one of the most critical structure of a cell, the disruption in membranes has a dramatic influence on cell function, which has been demonstrated in numerous studies (McNeil & Steinhardt, 2003). In terms of lipid-derived mediators, eicosanoid, and endocannabinoid have been shown to play key roles in skin function, especially GSK2879552 (Kendall & Nicolaou, 2013).
    The modulating role of fatty acids and sterols on skin aging Although sebaceous and epidermal lipids are mostly dependent on local lipogenesis (Feingold, 2007, Feingold, 2009), the supplementation of certain fatty acids and sterols has been shown to influence the process of skin aging (Latreille et al., 2012, Tanaka et al., 2016). A lower dietary intake of fat has been reported to be correlated with improved skin aging appearance in women aged 40–74 years in terms of wrinkleand skin atrophy (Cosgrove, Franco, Granger, Murray, & Mayes, 2007). However, the effect of specific type of fatty acids and sterols on skin aging differs. It also should be noted that the effect of topical and oral administration of a fatty acid or sterol might be different as the result of incomparable skin concentration reached.
    Concluding remarks The lipid content is altered in aged skin and the regulating effect of fatty acids/sterols on skin aging is complex. A higher dietary intake of fat is believed to be positively associated with skin aging (Cosgrove et al., 2007). The dietary supplementation of certain fatty acids (such as AA and PA) appears to augment skin aging. In addition, the dietary intakes of SFA and cholesterol were correlated with higher risk of cardiovascular diseases in some studies (Hooper et al., 2015, Kratz, 2005), although it is on debate (Kratz, 2005). However, the topical application of α-lipoic acid (a SFA) and cholesterol/phytosterols seems to be beneficial to aged skin. Furthermore, the dietary and topical application of some other lipids, such as n-3 PUFA, are believed to improve aged skin, suggesting it might be promising to enrich fatty acid/sterols with therapeutic benefits and limit harmful ones. Further studies focused on the alteration of fatty acid composition in aged skin is warranted.
    Funding This work was supported by the Natural Sciences and Engineering Research Council of Canada and Egg Farmers of Canada.
    Declaration of interests
    Ethics statement
    GPR84 belongs to the G protein-coupled receptor family, and it was first identified from human peripheral blood neutrophils [,]. GPR84 is now considered to be a member of receptor for medium chain fatty acid (MCFA) with carbon chain lengths of 9–14 []. GPR84 is mainly expressed in bone marrow, spleen, lung, lymph nodes, thymus and peripheral blood leukocytes of mice and is indicated to function as an immune cell-specific receptor for free fatty acids (FFA) [,]. The GPR84 activation in macrophages amplifies LPS-stimulated IL-12 p40 production [], and a study using -deficient mice also revealed a role of in the regulation of gene expression in activated T cells []. Furthermore, GPR84 agonist can upregulate the Akt, ERK, and NF-κB signaling pathways, and increase bacterial adhesion and phagocytosis in murine macrophages []. In addition, GPR84-deficient mice exhibited smaller livers and increased triglyceride accumulation in response to FFA diet [].