Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA<sub>2</sub>)

Markovics, Arnold; Tóth, Kinga Fanni; Sos, Katalin E.; Magi, József; Gyöngyösi, Adrienn; Benyó, Zoltán; Zouboulis, Christos C.; Bı́ró, Tamás; Oláh, Attila

doi:10.1111/jcmm.14505

Cited by 21 publications

(27 citation statements)

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“…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).…”

Section: Oea Promotes Differentiation Of Human Sebocytessupporting

confidence: 65%

“…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.…”

Section: Ethical Approvalmentioning

confidence: 95%

“…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.…”

Section: Oea Promotes Differentiation Of Human Sebocytesmentioning

confidence: 99%

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GPR119 Is a Potent Regulator of Human Sebocyte Biology

Markovics

Angyal

Tóth

et al. 2020

Journal of Investigative Dermatology

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We have shown previously that endocannabinoids promote sebaceous lipogenesis, and sebocytes are involved in the metabolism of the endocannabinoid-like substance oleoylethanolamide (OEA). OEA is an endogenous activator of GPR119, a recently deorphanized receptor, which currently is being investigated as a promising antidiabetic drug target. In this study, we investigated the effects of OEA as well as the expression and role of GPR119 in human sebocytes. We found that OEA promoted differentiation of human SZ95 sebocytes (elevated lipogenesis, enhanced granulation, and the induction of early apoptotic events), and it switched the cells to a proinflammatory phenotype (increased expression and release of several proinflammatory cytokines). Moreover, we could also demonstrate that GPR119 was expressed in human sebocytes, and its small interfering RNAemediated gene silencing suppressed OEA-induced sebaceous lipogenesis, which was mediated via c-Jun N-terminal kinase, extracellular signaleregulated kinase 1/2, protein kinase B, and CRE-binding protein activation. Finally, our pilot data demonstrated that GPR119 was downregulated in the sebaceous glands of patients with acne, arguing that GPR119 signaling may indeed be disturbed in acne. Collectively, our findings introduce the OEA/GPR119 signaling as a positive regulator of sebocyte differentiation and highlight the possibility that dysregulation of this pathway may contribute to the development of seborrhea and acne.

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Section: Oea Promotes Differentiation Of Human Sebocytessupporting

confidence: 65%

Section: Ethical Approvalmentioning

confidence: 95%

Section: Oea Promotes Differentiation Of Human Sebocytesmentioning

confidence: 99%

See 1 more Smart Citation

GPR119 Is a Potent Regulator of Human Sebocyte Biology

Markovics

Angyal

Tóth

et al. 2020

Journal of Investigative Dermatology

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Zhao

Jia-fei

Yin

et al. 2019

Food and Agricultural Immunology

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In this study, we determined the nutritional and functional components in blossom and bee pollen from Rosa rugosa and evaluated their effects on acne caused by excessive androgen secretion based on the golden hamster acne model. Blossom and bee pollen extract from Rosa rugosa had beneficial effects on reducing the area of the sebaceous glands, decreasing TG levels in the sebaceous glands, decreasing the release of IL-1α and TNFα, alleviating the release of MMP-2 and MMP-9, increasing the content of caspase-3, reducing the release of testosterone T, and increasing the release of estrogen E 2. Both blossom and bee pollen extract from Rosa rugosa could alleviate acne caused by excessive androgenic secretion. In addition, bee pollen extract may have better effects on alleviating the release of inflammatory cytokines and MMPs, and promoting the degree of apoptosis. However, blossom extract may have better effects on regulating the levels of sex hormone.

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“…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).…”

Section: Methodsmentioning

confidence: 99%

Allithiamine Alleviates Hyperglycaemia-Induced Endothelial Dysfunction

et al. 2020

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Diabetes mellitus-related morbidity and mortality is a rapidly growing healthcare problem, globally. Several nutraceuticals exhibit potency to target the pathogenesis of diabetes mellitus. The antidiabetic effects of compounds of garlic have been extensively studied, however, limited data are available on the biological effects of a certain garlic component, allithiamine. In this study, allithiamine was tested using human umbilical cord vein endothelial cells (HUVECs) as a hyperglycaemic model. HUVECs were isolated by enzymatic digestion and characterized by flow cytometric analysis using antibodies against specific marker proteins including CD31, CD45, CD54, and CD106. The non-cytotoxic concentration of allithiamine was determined based on MTT, apoptosis, and necrosis assays. Subsequently, cells were divided into three groups: incubating with M199 medium as the control; or with 30 mMol/L glucose; or with 30 mMol/L glucose plus allithiamine. The effect of allithiamine on the levels of advanced glycation end-products (AGEs), activation of NF-κB, release of pro-inflammatory cytokines including IL-6, IL-8, and TNF-α, and H2O2-induced oxidative stress was investigated. We found that in the hyperglycaemia-induced increase in the level of AGEs, pro-inflammatory changes were significantly suppressed by allithiamine. However, allithiamine could not enhance the activity of transketolase, but it exerts a potent antioxidant effect. Collectively, our data suggest that allithiamine could alleviate the hyperglycaemia-induced endothelial dysfunction due to its potent antioxidant and anti-inflammatory effect by a mechanism unrelated to the transketolase activity.

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

Cited by 21 publications

References 56 publications

GPR119 Is a Potent Regulator of Human Sebocyte Biology

GPR119 Is a Potent Regulator of Human Sebocyte Biology

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

Allithiamine Alleviates Hyperglycaemia-Induced Endothelial Dysfunction

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

Cited by 21 publications

References 56 publications

GPR119 Is a Potent Regulator of Human Sebocyte Biology

GPR119 Is a Potent Regulator of Human Sebocyte Biology

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

Allithiamine Alleviates Hyperglycaemia-Induced Endothelial Dysfunction

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