Adipokines are the primary mediators of adipose tissue-induced and regulated systemic inflammatory diseases; however, recent findings revealed that serum levels of various adipokines correlate also with the onset and the severity of dermatological diseases. Importantly, further data confirmed that the skin serves not only as a target for adipokine signaling, but may serve as a source too. In this review, we aim to provide a complex overview on how adipokines may integrate into the (patho) physiological conditions of the skin by introducing the cell types, such as keratinocytes, fibroblasts, and sebocytes, which are known to produce adipokines as well as the signals that target them. Moreover, we discuss data from in vivo and in vitro murine and human studies as well as genetic data on how adipokines may contribute to various aspects of the homeostasis of the skin, e.g., melanogenesis, hair growth, or wound healing, just as to the pathogenesis of dermatological diseases such as psoriasis, atopic dermatitis, acne, rosacea, and melanoma.

Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options.

Alcohol affects the symptoms, compliance and comorbidities as well as the safety and efficacy of treatments in psoriatic patients. In this review, we aim to summarize and link clinical observations with a molecular background, such as signaling pathways at the cellular level and genetic variations, and to provide an overview of how this knowledge could influence our treatment selection and patient management.

In a recently published research letter Burney et al. demonstrated that isotretinoin (13‐cis‐retinoic acid, 13CRA) induced acnegenic changes in SEB‐1 cultured human sebocytes¹. However, Melnik et al., suggested that the observed changes may largely be influenced by the Simian virus (SV)‐40 immortalization of the used cell line, which may inhibit the p53 pathway and together with 13CRA lead to changes, such as the down‐regulation of the forkhead box O (FoxO) pathway. In contrast, they found that the FoxO pathway was upregulated in samples from patients receiving 13CRA treatment for 6 weeks.

Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14), p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors.

Background/Objectives: Sebocytes, the primary cell type in sebaceous glands (SGs), produce a lipid mixture called sebum that is released onto the skin surface and is required for skin homeostasis. The lipid receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) regulates sebocyte proliferation and lipid synthesis and is involved in acne development. As inhibition of PPARγ has been shown to reduce insulin-induced lipogenesis and Akt/mTOR signalling in SZ95 sebocytes, we here investigated the effects of PPARγ deletion on lipid homeostasis and autophagic stress responses and how the secretomes affect dermal fibroblasts. Methods: SZ95 sebocytes wildtype (WT) and PPARγ knockout (KO) were shifted to low serum and EGF-deficient conditions permissive for autophagy. Untargeted and targeted HPLC-MS/MS analyses were used to analyze native and oxidized lipids, respectively. Protein levels of LC3I/II and p62 were assessed using immunoblots and immunofluorescence microscopy to investigate the autophagic flux. Dermal fibroblasts were exposed to conditioned media. Results: In low serum culture media, KO SZ95 sebocytes displayed significantly altered levels of 23 lipid classes. We observed a significant increase in ether-linked fatty acids as components of complex lipids and detected elevated levels of phospholipid hydroperoxides and aldehydolipids in the KO sebocytes. KO SZ95 sebocytes failed to show the typical responses to lipoxidative stress, such as elevated p62 crosslinking or inclusion body formation, and had reduced LC3II/I ratios as compared to WT cells. PPARγ KO conditioned media promoted a trend towards an inflammatory fibroblast phenotype. Conclusions: These findings suggest that PPARγ in sebocytes may alter the lipidome, elevate redox stress, and affect the autophagic machinery, which could cause accumulation of oxidized lipids and other potentially harmful compounds in sebocytes.