GPR119 Is a Potent Regulator of Human Sebocyte Biology

Arnold Markovics, Ágnes Angyal, Kinga Fanni Tóth, Dorottya Ádám, Zsófia Pénzes, József Magi, Ágnes Pór, Ilona Kovács, Dániel Törőcsik, Christos C. Zouboulis, Tamás Bíró, Attila Oláh

Research output: Contribution to journalArticle

Abstract

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 RNA–mediated gene silencing suppressed OEA-induced sebaceous lipogenesis, which was mediated via c-Jun N-terminal kinase, extracellular signal–regulated 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.

Original languageEnglish
JournalJournal of Investigative Dermatology
DOIs
Publication statusAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Markovics, A., Angyal, Á., Tóth, K. F., Ádám, D., Pénzes, Z., Magi, J., Pór, Á., Kovács, I., Törőcsik, D., Zouboulis, C. C., Bíró, T., & Oláh, A. (Accepted/In press). GPR119 Is a Potent Regulator of Human Sebocyte Biology. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2020.02.011