Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA2 ).

Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA2 ), and it is widely used in treating dyslipidaemias. Since its side effects include skin dryness, whereas its deficiency can be accompanied by dyssebacia, characterized by sebaceous gland enlargement, we asked if HCA2 is expressed on human sebocytes, and if NA influences sebocyte functions. By using human immortalized SZ95 sebocytes, we found that non-cytotoxic (≤100 µmol/L; MTT-assay) concentrations of NA had no effect on the homeostatic sebaceous lipogenesis (SLG; Nile Red), but normalized excessive, acne-mimicking SLG induced by several lipogenic agents (arachidonic acid, anandamide, linoleic acid + testosterone; Nile Red; 48-hr treatments). Moreover, it exerted significant anti-proliferative actions (CyQUANT-assay), and increased [Ca2+ ]IC (Fluo-4 AM-based Ca2+ -measurement). Although NA did not prevent the lipopolysaccharide-induced pro-inflammatory response (up-regulation [Q-PCR] and release [ELISA] of several pro-inflammatory cytokines) of the sebocytes, collectively, these data support the concept that NA may be effective in suppressing sebum production in vivo. While exploring the mechanism of the sebostatic actions, we found that sebocytes express HCA2 (Q-PCR, immunofluorescent labelling), siRNA-mediated silencing of which prevented the NA-induced Ca2+ -signal and the lipostatic action. Collectively, our data introduce NA, and HCA2 activators in general, as novel, potent and most likely safe sebostatic agents, with possible anti-acne potential.

Topical application of autophagy-activating peptide improved skin barrier function and reduced acne symptoms in acne-prone skin.

BACKGROUND: Recent studies about the important roles of autophagy signaling in sebaceous lipogenesis and epidermal differentiation suggest potential benefits of autophagy activation in acne. AIMS: To investigate the effects of an autophagy activator on acne-prone skin. METHODS: Autophagy signaling in human immortalized SZ95 sebocytes, normal human epidermal keratinocytes, and 3D reconstituted skin was examined. Effects of an autophagy-activating peptide on sebaceous lipogenesis were measured by fluorescence microscopic analysis. The clinical efficacy in acne-prone skin was evaluated through an eight-week, double-blind, randomized, vehicle-controlled study. Changes in skin surface lipid compositions were further analyzed. RESULTS: In cultured sebocytes and keratinocytes, the investigated autophagy-activating peptide increased LC3-II expression, indicating a stimulation of autophagy signaling. Testosterone and linoleic acid treatment induced lipogenesis in cultured sebocytes and is further inhibited by the autophagy activator peptide treatment. Increased expression of differentiation marker proteins in cultured keratinocytes was also observed by autophagy-activating peptide. In clinical study, reduction of closed comedones and the amount of skin surface lipids as well as of trans-epidermal water loss (TEWL) were observed in acne-prone skin after autophagy-activating peptide application. In addition, reduction of squalene and increase in cholesterol were observed after an 8-week application. CONCLUSIONS: Topical application of an autophagy activator downregulated sebaceous lipogenesis and improved the skin barrier function. Considering the important roles of sebum and skin barrier function in acne pathogenesis, autophagy activation might represent a new therapeutic option in early forms of acne.

EGFR/ERBB receptors differentially modulate sebaceous lipogenesis.

The roles of the epidermal growth factor receptor (EGFR) in sebaceous glands remain poorly explored. We show that human sebocytes express EGFR and lower levels of ERBB2 and ERBB3, all receptors being downregulated after the induction of lipid synthesis. Nile red staining showed that siRNA-mediated downregulation of EGFR or ERBB3 increases lipid accumulation, whereas ERBB2 downregulation has no effect. Spectrometry confirmed induction of triglycerides after EGFR or ERBB3 downregulation and revealed induction of cholesteryl esters after downregulation of EGFR, ERBB2 or ERBB3. Thus, EGFR/ERBB receptors differentially modulate sebaceous lipogenesis, a key feature of sebaceous gland physiology and of several skin diseases.