GPR119 Is a Potent Regulator of Human Sebocyte Biology

Markovics, Arnold and Angyal, Ágnes and Tóth, Kinga Fanni and Ádám, Dorottya and Pénzes, Zsófia and Magi, József and Pór, Ágnes and Kovács, Ilona and Törőcsik, Dániel and Zouboulis, Christos C. and Bíró, Tamás and Oláh, Attila (2020) GPR119 Is a Potent Regulator of Human Sebocyte Biology. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 140 (10). pp. 1909-1918. ISSN 0022-202X

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Abstract

We have previously shown 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 de-orphanized receptor, which is currently being investigated as a promising anti-diabetic drug target. Thus, in the current 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 pro-inflammatory phenotype (increased expression and release of several pro-inflammatory cytokines). Moreover, we could also demonstrate that GPR119 was expressed in human sebocytes, and its siRNA-mediated gene silencing suppressed OEA-induced sebaceous lipogenesis, which was mediated via JNK, ERK1/2, Akt/PKB, and CREB activation. Finally, our pilot data demonstrated that GPR119 was down-regulated in sebaceous glands of acne patients, arguing that GPR119 signaling may indeed be disturbed in acne. Collectively, our findings introduce the OEAGPR119 signaling as a new 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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