Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
State Key Laboratory of Biochemical Engineering and Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Mar Drugs. 2018 Nov 19;16(11):455. doi: 10.3390/md16110455.
Chitosan oligosaccharides (COS) display various biological activities. In this study, we aimed to explore the preventive effects of COS on glucolipid metabolism disorder using palmitic acid (PA)-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6J mice as experimental models in vitro and in vivo, respectively. The results showed that COS pretreatment for 12 h significantly ameliorated lipid accumulation in HepG2 cells exposed to PA for 24 h, accompanied by a reversing of the upregulated mRNA expression of proinflammatory cytokines (IL-6, MCP-1, TNF-α) and glucolipid metabolism-related regulators (SCD-1, ACC1, PCK1-α). In addition, COS treatment alleviated glucolipid metabolism disorder in mice fed with HFD for five months, including reduction in body weight and fasting glucose, restoration of intraperitoneal glucose tolerance, and suppression of overexpression of proinflammatory cytokines and glucolipid metabolism-related regulators. Furthermore, our study found that COS pretreatment significantly reversed the downregulation of PPARγ at transcriptional and translational levels in both PA-induced HepG2 cells and liver tissues of HFD-fed mice. In summary, the study suggests that COS can improve glucolipid metabolism disorder by suppressing inflammation and upregulating PPARγ expression. This indicates a novel application of COS in preventing and treating glucolipid metabolism-related diseases.
壳寡糖（COS）具有多种生物学活性。本研究旨在通过体外（PA 诱导的 HepG2 细胞）和体内（HFD 喂养的 C57BL/6J 小鼠）实验模型，分别探讨 COS 对糖脂代谢紊乱的预防作用。结果表明，COS 预处理 12 h 可显著改善 PA 处理 24 h 的 HepG2 细胞中的脂质积累，同时上调促炎细胞因子（IL-6、MCP-1、TNF-α）和糖脂代谢相关调节因子（SCD-1、ACC1、PCK1-α）的 mRNA 表达。此外，COS 处理可减轻 HFD 喂养五个月小鼠的糖脂代谢紊乱，包括体重和空腹血糖降低、腹腔内葡萄糖耐量恢复以及抑制促炎细胞因子和糖脂代谢相关调节因子的过度表达。此外，本研究发现，COS 预处理可显著逆转 PA 诱导的 HepG2 细胞和 HFD 喂养小鼠肝组织中 PPARγ 在转录和翻译水平的下调。综上所述，COS 可通过抑制炎症和上调 PPARγ 表达来改善糖脂代谢紊乱，为 COS 在预防和治疗糖脂代谢相关疾病方面的应用提供了新的思路。
