Pyun Do Hyeon, Kim Tae Jin, Park Seung Yeon, Lee Hyun Jung, Abd El-Aty A M, Jeong Ji Hoon, Jung Tae Woo
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea.
Mol Cell Endocrinol. 2021 Dec 1;538:111464. doi: 10.1016/j.mce.2021.111464. Epub 2021 Sep 30.
Obesity-induced chronic low-grade inflammation and thus causes various metabolic diseases, such as insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patchouli alcohol (PA), an active component extracted from patchouli, displayed anti-inflammatory effects on different cell types. However, the impact of PA on skeletal muscle insulin signaling and hepatic lipid metabolism remains unclear. This study aimed to investigate whether PA would affect insulin signaling impairment in myocytes and lipid metabolism in hepatocytes. Treatment with PA ameliorated palmitate-induced inflammation and aggravation of insulin signaling in C2C12 myocytes and lipid accumulation in HepG2 hepatocytes. Treatment of C2C12 myocytes and HepG2 cells with PA augmented AMP-activated protein kinase (AMPK) phosphorylation and Sirtuin 1 (SIRT1) expression in a dose-dependent manner. siRNA-mediated suppression of AMPK or SIRT1 mitigated the effects of PA on palmitate-induced inflammation and insulin resistance in C2C12 myocytes and lipid accumulation in HepG2 cells. Animal experiments demonstrated that PA administration increased AMPK phosphorylation and SIRT1 expression, and ameliorated inflammation, thereby attenuating skeletal muscle insulin resistance and hepatic steatosis in high-fat diet-fed mice. These results denote that PA alleviates skeletal muscle insulin resistance and hepatic steatosis through AMPK/SIRT1-dependent signaling. This study might provide a novel therapeutic approach for treating obesity-related insulin resistance and NAFLD.
肥胖会引发慢性低度炎症，进而导致各种代谢性疾病，如胰岛素抵抗和非酒精性脂肪性肝病（NAFLD）。广藿香醇（PA）是从广藿香中提取的一种活性成分，对不同细胞类型具有抗炎作用。然而，PA对骨骼肌胰岛素信号传导和肝脏脂质代谢的影响仍不清楚。本研究旨在探讨PA是否会影响心肌细胞中的胰岛素信号传导损伤以及肝细胞中的脂质代谢。用PA处理可改善棕榈酸酯诱导的C2C12心肌细胞炎症和胰岛素信号传导加重以及HepG2肝细胞中的脂质积累。用PA处理C2C12心肌细胞和HepG2细胞可剂量依赖性地增强AMP激活的蛋白激酶（AMPK）磷酸化和沉默调节蛋白1（SIRT1）表达。siRNA介导的AMPK或SIRT1抑制减轻了PA对棕榈酸酯诱导的C2C12心肌细胞炎症和胰岛素抵抗以及HepG2细胞脂质积累的影响。动物实验表明，给予PA可增加AMPK磷酸化和SIRT1表达，并改善炎症，从而减轻高脂饮食喂养小鼠的骨骼肌胰岛素抵抗和肝脏脂肪变性。这些结果表明，PA通过AMPK/SIRT1依赖性信号传导减轻骨骼肌胰岛素抵抗和肝脏脂肪变性。本研究可能为治疗肥胖相关的胰岛素抵抗和NAFLD提供一种新的治疗方法。
