Open AccessNicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA 2 )
Author(s) -
Markovics Arnold,
Tóth Kinga Fanni,
Sós Katalin Eszter,
Magi József,
Gyöngyösi Adrienn,
Benyó Zoltán,
Zouboulis Christos C.,
Bíró Tamás,
Oláh Attila
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14505
Subject(s) - lipogenesis , sebaceous gland , chemistry , arachidonic acid , linoleic acid , endocrinology , medicine , nile red , lipopolysaccharide , nicotinic agonist , receptor , adipose tissue , fatty acid , biochemistry , biology , enzyme , physics , quantum mechanics , fluorescence
Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA 2 ), 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 HCA 2 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 [Ca 2+ ] IC (Fluo‐4 AM‐based Ca 2+ ‐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 HCA 2 (Q‐PCR, immunofluorescent labelling), siRNA‐mediated silencing of which prevented the NA‐induced Ca 2+ ‐signal and the lipostatic action. Collectively, our data introduce NA, and HCA 2 activators in general, as novel, potent and most likely safe sebostatic agents, with possible anti‐acne potential.