Institute of Hansen's Disease, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea.
Arch Dermatol Res. 2014 May;306(4):339-45. doi: 10.1007/s00403-013-1434-6. Epub 2013 Dec 15.
It has been suggested that free fatty acids (FFA) such as palmitate, which are secreted from enlarged adipocytes in the subcutaneous fat of obese subjects, serve as a link between obesity and altered skin functions. Cyclooxygenease-2 (COX-2) and prostanoids participate in the induction of impaired dermal function. In the current study, we investigated the issue of whether palmitate induces COX-2 expression via the sphingolipid pathway-mediated activation of NF-κB or mitogen-activated protein kinase (MAPK) pathways in human dermal fibroblasts. Palmitate treatment significantly induced COX-2 expression and prostaglandin E2 (PGE2) release in human dermal fibroblasts. In addition, pre-treatment with triacsin C, an inhibitor of acyl-CoA synthetase in de novo ceramide synthesis, was found to reduce palmitate-induced COX-2 expression and PGE2 release in human dermal fibroblast. The findings also show that palmitate-induced COX-2 expression and PGE2 release are mediated by the NF-κB, p38, and extracellular signal-regulated kinase (ERK) MAPK pathways. These findings point to a new mechanism for explaining the link between increased FFAs in obesity and impaired dermal function.
有人提出，肥胖患者皮下脂肪组织中肥大的脂肪细胞分泌的游离脂肪酸（FFA），如棕榈酸，可能是肥胖与皮肤功能改变之间的联系。环氧化酶-2（COX-2）和前列腺素参与诱导皮肤功能障碍。在本研究中，我们研究了棕榈酸是否通过鞘脂途径介导的 NF-κB 或丝裂原活化蛋白激酶（MAPK）途径激活诱导人真皮成纤维细胞中 COX-2 表达。棕榈酸处理可显著诱导人真皮成纤维细胞中 COX-2 表达和前列腺素 E2（PGE2）释放。此外，发现酰基辅酶 A 合成酶抑制剂三乙酰精氨酸 C 预处理可降低人真皮成纤维细胞中棕榈酸诱导的 COX-2 表达和 PGE2 释放。研究结果还表明，棕榈酸诱导的 COX-2 表达和 PGE2 释放是由 NF-κB、p38 和细胞外信号调节激酶（ERK）MAPK 途径介导的。这些发现为解释肥胖症中游离脂肪酸增加与皮肤功能障碍之间的联系提供了一种新的机制。
