Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Korea.
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon 21999, Korea.
Mar Drugs. 2021 Aug 30;19(9):495. doi: 10.3390/md19090495.
Increased inflammation is the main pathophysiology of nonalcoholic fatty liver disease (NAFLD). Inflammation affects lymphatic vessel function that contributes to the removal of immune cells or macromolecules. Dysfunctional lymphatic vessels with decreased permeability are present in NAFLD. High-fat diet (HFD) is known to increase body weight, food intake, and inflammation in the liver. Previously, it was reported that extracts (ECE) decreased food intake or weight gain, and low-calorie diet and weight loss is known as a treatment for NAFLD. In this study, the effects of ECE and dieckol (DK)-which is one component of ECE that decreases inflammation and increases lymphangiogenesis and lymphatic drainage by controlling lymphatic permeability in high-fat diet (HFD)-fed mice-on weight gain and food intake were investigated. ECE and DK decreased weight gain and food intake in the HFD-fed mice. NAFLD activities such as steatosis, lobular inflammation, and ballooning were increased by HFD and attenuated by ECE and DK. The expression of inflammatory cytokines such as IL-6 and TNF-α and infiltration of M1 macrophages were increased by HFD, and they were decreased by ECE or DK. The signaling pathways of lymphangiogenesis, VEGFR-3, PI3K/pAKT, and pERK were decreased by HFD, and they were restored by either ECE or DK. The expression of VE-cadherin (which represents lymphatic junctional function) was increased by HFD, although it was restored by either ECE or DK. In conclusion, ECE and DK attenuated NAFLD by decreasing weight gain and food intake, decreasing inflammation, and increasing lymphangiogenesis, as well as modulating lymphatic vessel permeability.
炎症增加是非酒精性脂肪性肝病（NAFLD）的主要病理生理学机制。炎症会影响淋巴管的功能，从而影响免疫细胞或大分子的清除。NAFLD 存在功能失调的、通透性降低的淋巴管。高脂肪饮食（HFD）已知会增加体重、食物摄入和肝脏炎症。先前有报道称，提取物（ECE）可减少食物摄入或体重增加，而低热量饮食和减肥是治疗 NAFLD 的方法。在这项研究中，研究了 ECE 和二酮（DK）对高脂肪饮食（HFD）喂养的小鼠体重增加和食物摄入的影响。ECE 和 DK 可降低 HFD 喂养的小鼠的体重增加和食物摄入。ECE 和 DK 可减轻 HFD 引起的肝脂肪变性、小叶炎症和气球样变等 NAFLD 活动。ECE 或 DK 可降低 HFD 引起的炎症细胞因子（如 IL-6 和 TNF-α）的表达和 M1 巨噬细胞的浸润。HFD 会降低淋巴管生成的信号通路，如 VEGFR-3、PI3K/pAKT 和 pERK，而 ECE 或 DK 可恢复这些信号通路。HFD 会增加 VE-钙黏蛋白（代表淋巴管连接功能）的表达，但 ECE 或 DK 可恢复其表达。总之，ECE 和 DK 通过降低体重增加和食物摄入、减少炎症和增加淋巴管生成以及调节淋巴管通透性来减轻 NAFLD。
