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

Arnold Markovics, Kinga Fanni Tóth, Katalin Eszter Sós, József Magi, Adrienn Gyöngyösi, Zoltán Benyó, Christos C. Zouboulis, Tamás Bíró, Attila Oláh

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6203-6214
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number9
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • acne
  • hydroxycarboxylic acid receptor 2
  • nicotinic acid
  • sebaceous lipogenesis
  • sebocyte
  • seborrhea

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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