Lycopene prevents the progression of lipotoxicity-induced nonalcoholic steatohepatitis by decreasing oxidative stress in mice
Lycopene prevents the progression of lipotoxicity-induced nonalcoholic steatohepatitis by decreasing oxidative stress in mice
复制标题
番茄红素通过减少小鼠的氧化应激来预防脂毒性诱导的非酒精性脂肪性肝炎的进展
DOI：
10.1016/j.freeradbiomed.2019.11.036
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发表时间：
2020-05-20
影响因子：
7.4
通讯作者：
Ota, Tsuguhito
中科院分区：
文献类型：
--
作者：
Ni, Yinhua;Zhuge, Fen;Ota, Tsuguhito
过量脂肪酸摄入引起的氧化应激会导致肝损伤和炎症免疫细胞的连续募集，从而促进单纯性脂肪变性发展为非酒精性脂肪性肝炎（NASH）。番茄红素是抗氧化剂类胡萝卜素中最有效的单线态氧清除剂，具有抗炎活性。在这里，我们研究了番茄红素在 NASH 脂毒性模型中的预防和治疗作用：喂养高胆固醇和高脂肪饮食的小鼠。番茄红素缓解肝脏过度脂质堆积并增强脂肪分解，降低M1型巨噬细胞/枯否细胞的比例，并激活星状细胞以改善肝脏炎症和纤维化，从而减少肝脏中CD4+和CD8+T细胞的募集。重要的是，番茄红素可以逆转已有的 NASH 中的胰岛素抵抗以及肝脏炎症和纤维化。同时，番茄红素以剂量依赖性方式降低腹膜巨噬细胞中LPS-/IFN-α-/TNFα诱导的M1标记物mRNA水平，以及星状细胞系中TGF-β1诱导的纤维形成基因的表达。这些结果与细胞氧化应激减少有关，这可能是由 NADPH 氧化酶亚基的表达介导的。总之，番茄红素通过减少氧化应激来预防和逆转 NASH 小鼠中脂毒性诱导的炎症和纤维化。因此，它可能是一种新颖且有前途的 NASH 治疗方法。
Excessive fatty acid uptake -induced oxidative stress causes liver injury and the consecutive recruitment of in- flammatory immune cells, thereby promoting the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Lycopene, the most effective singlet oxygen scavenger of the antioxidant carotenoids, has anti-in- flammatory activity. Here, we investigated the preventive and therapeutic effects of lycopene in a lipotoxic model of NASH: mice fed a high -cholesterol and high -fat diet. Lycopene alleviated excessive hepatic lipid ac- cumulation and enhanced lipolysis, decreased the proportion of M1 -type macrophages/Kupffer cells, and acti- vated stellate cells to improve hepatic inflammation and fibrosis, and subsequently reduced the recruitment of CD4 + and CD8 + T cells in the liver. Importantly, lycopene reversed insulin resistance, as well as hepatic in- flammation and fibrosis, in pre-existing NASH. In parallel, lycopene decreased LPS-/IFN-?-/TNF?-induced M1 marker mRNA levels in peritoneal macrophages, as well as TGF-?1-induced expression of fibrogenic genes in a stellate cell line, in a dose -dependent manner. These results were associated with decreased oxidative stress in cells, which might be mediated by the expression of NADPH oxidase subunits. In summary, lycopene prevented and reversed lipotoxicity-induced inflammation and fibrosis in NASH mice by reducing oxidative stress. Therefore, it might be a novel and promising treatment for NASH.