Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments.
Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments.
复制标题
非酒精性脂肪肝和胰岛素抵抗：新的见解和潜在的新治疗方法。
作者：
Kitade H;Chen G;Ni Y;Ota T
非酒精性脂肪肝病（NAFLD）是世界范围内最常见的慢性肝病之一。它与肥胖、胰岛素抵抗和 2 型糖尿病等临床状态相关，涵盖多种肝脏变化，从单纯性脂肪变性到非酒精性脂肪性肝炎 (NASH)、肝硬化和肝细胞癌。脂质蓄积、胰岛素抵抗和炎症等代谢紊乱与 NAFLD 的发病机制有关，但其潜在机制，包括那些驱动疾病进展的机制，尚不完全清楚。先天和招募的免疫细胞都会介导胰岛素抵抗和 NASH 的发展。因此，改变常驻和招募的巨噬细胞/库普弗细胞的极化有望带来 NAFLD 的新治疗策略。氧化应激对于 NASH 的进展也至关重要，这引起了人们对类胡萝卜素作为治疗 NAFLD 的有效微量营养素抗氧化剂的兴趣。除了抗氧化功能外，类胡萝卜素还调节巨噬细胞/库普弗细胞极化，从而防止 NASH 进展。在这篇综述中，我们总结了 NAFLD 发病机制中涉及的分子机制，包括 NAFLD 中的巨噬细胞/库普弗细胞极化和肝功能紊乱。我们还讨论了膳食抗氧化剂，例如 β-隐黄素和虾青素，它们可能有效预防或治疗 NAFLD。
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood. Both innate and recruited immune cells mediate the development of insulin resistance and NASH. Therefore, modifying the polarization of resident and recruited macrophage/Kupffer cells is expected to lead to new therapeutic strategies in NAFLD. Oxidative stress is also pivotal for the progression of NASH, which has generated interest in carotenoids as potent micronutrient antioxidants in the treatment of NAFLD. In addition to their antioxidative function, carotenoids regulate macrophage/Kupffer cell polarization and thereby prevent NASH progression. In this review, we summarize the molecular mechanisms involved in the pathogenesis of NAFLD, including macrophage/Kupffer cell polarization, and disturbed hepatic function in NAFLD. We also discuss dietary antioxidants, such as β-cryptoxanthin and astaxanthin, that may be effective in the prevention or treatment of NAFLD.