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

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.

GPR119 Is a Potent Regulator of Human Sebocyte Biology

“…These data suggested that, similar to the classical eCBs (Dobrosi et al, 2008;Zákány et al, 2018), OEA is also able to promote differentiation of human sebocytes. Lipogenic potential of OEA was comparable to the ones typically seen in case of classical eCBs (e.g., AEA [30 mM]), arachidonic acid (50 mM), or the combination of linoleic acid and testosterone (100 mM and 1 mM, respectively, 48-hour treatments; Figure 1d) (Dobrosi et al, 2008;Géczy et al, 2012;Makrantonaki and Zouboulis, 2007;Markovics et al, 2019;Oláh et al, 2016b;Oláh et al, 2014;Szántó et al, 2019;Tó th et al, 2009;Zákány et al, 2018).…”

“…Detailed descriptions of the methods to assess sebaceous lipogenesis (Nile Red), differentiation-associated granulation (flow cytometry), viability (MTT assay), cell death (DilC 1 (5)-SYTOX Green labeling), proliferation (CyQUANT assay), Ca 2þ homeostasis (Fluo-4 AMebased fluorescent Ca 2þ -measurement), gene expression at the mRNA (Q-PCR) and protein levels (western blot, immunohistochemistry, and ELISA), and small interfering RNAemediated silencing can be found in our previous publications (Lisztes et al, 2019;Markovics et al, 2019;Oláh et al, 2017a;Oláh et al, 2016a;Oláh et al, 2014;Ramot et al, 2018;Szabó et al, 2020) and in the Supplementary Materials and Methods.…”

“…Classical eCBs (i.e., AEA and 2-arachidonoylglycerol) as well as arachidonic acid typically promote sebaceous lipogenesis of SZ95 sebocytes at 30e50 mM in the course of 24-to 48-hour treatments (Dobrosi et al, 2008;Géczy et al, 2012;Markovics et al, 2019;Oláh et al, 2016b;Oláh et al, 2014;Szántó et al, 2019;Tóth et al, 2009;Zákány et al, 2018). First, we tested the effects of OEA at the 10 nMe50 mM concentration range.…”

Blossom and bee pollen from Rosa rugosa as potential intervention for acne caused by excessive androgen secretion in golden hamster acne model

“…An important sign in the onset of acne lesions is that the hair follicle sebaceous gland unit can induce inflammation (Zouboulis, 2004) and is always accompanied by inflammatory responses during acne (Roodsari et al, 2010). IL-1α, IL-6 and TNF-α are the major cytokines of inflammation in the body, which can stimulate the proliferation and sebum production of sebocytes (Markovics et al, 2019). Ji found that the content of IL-1α and IL-6 in serum cytokines from patients were significantly higher than normal people (Ji et al, 2018).…”

Allithiamine Alleviates Hyperglycaemia-Induced Endothelial Dysfunction

“…The mitochondrial membrane potential of the HUVECs was determined by using 1,1′,3,3,3′,3′-hexamethylindodicarbocyanin iodide (DilC 1 (5)) dye. The decrease in the DilC 1 (5) intensity indicated mitochondrial depolarization, i.e., the onset of early apoptotic processes of HUVECs [ 23 , 24 ]. Cells were seeded to 96-well plates at a density of 20,000 cells per well treated with allithiamine of different concentrations (0.1, 0.5, 1, 5, 10, and 50 μg/mL).…”