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.

以前我们已经表明，内源性大麻素可促进皮脂的脂肪生成，皮脂细胞参与内源性大麻素样物质油酰乙醇酰胺（OEA）的代谢。OEA是GPR119的内源性激活剂，GPR119是一种最近被脱孤的受体，目前正被研究为有希望的抗糖尿病药物靶标。在这项研究中，我们调查了OEA的作用以及GPR119在人皮脂细胞中的表达和作用。我们发现，OEA促进了人类SZ95皮脂细胞的分化（脂肪生成增加，肉芽形成和早期凋亡事件的诱导），并且将细胞切换为促炎表型（增加了几种促炎细胞因子的表达和释放）。此外，我们还可以证明GPR119在人类皮脂细胞中表达，它的小干扰RNA介导的基因沉默抑制了OEA诱导的皮脂脂生成，这是通过c-Jun N端激酶，细胞外信号调节激酶1/2，蛋白激酶B和CRE结合蛋白激活介导的。最后，我们的试验数据表明痤疮患者皮脂腺中的GPR119被下调，认为GPR119信号确实可能在痤疮中受到干扰。总的来说，我们的发现引入了OEA / GPR119信号作为皮脂细胞分化的正调节剂，并突显了这种途径的失调可能有助于皮脂溢和痤疮的发展。和CRE结合蛋白激活。最后，我们的试验数据表明痤疮患者皮脂腺中的GPR119被下调，认为GPR119信号确实可能在痤疮中受到干扰。总的来说，我们的发现引入了OEA / GPR119信号作为皮脂细胞分化的正调节剂，并突显了这种途径的失调可能有助于皮脂溢和痤疮的发展。和CRE结合蛋白激活。最后，我们的试验数据表明痤疮患者皮脂腺中的GPR119被下调，认为GPR119信号确实可能在痤疮中受到干扰。总的来说，我们的发现引入了OEA / GPR119信号作为皮脂细胞分化的正调节剂，并突显了这种途径的失调可能有助于皮脂溢和痤疮的发展。