Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
Front Endocrinol (Lausanne). 2020 Nov 26;11:597583. doi: 10.3389/fendo.2020.597583. eCollection 2020.
Obesity, diabetes, insulin resistance, sedentary lifestyle, and Western diet are the key factors underlying non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases in developed countries. In many cases, NAFLD further progresses to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and to hepatocellular carcinoma. The hepatic lipotoxicity and non-liver factors, such as adipose tissue inflammation and gastrointestinal imbalances were linked to evolution of NAFLD. Nowadays, the degree of adipose tissue inflammation was shown to directly correlate with the severity of NAFLD. Consumption of higher caloric intake is increasingly emerging as a fuel of metabolic inflammation not only in obesity-related disorders but also NAFLD. However, multiple causes of NAFLD are the reason why the mechanisms of NAFLD progression to NASH are still not well understood. In this review, we explore the role of food intake regulating peptides in NAFLD and NASH mouse models. Leptin, an anorexigenic peptide, is involved in hepatic metabolism, and has an effect on NAFLD experimental models. Glucagon-like peptide-1 (GLP-1), another anorexigenic peptide, and GLP-1 receptor agonists (GLP-1R), represent potential therapeutic agents to prevent NAFLD progression to NASH. On the other hand, the deletion of ghrelin, an orexigenic peptide, prevents age-associated hepatic steatosis in mice. Because of the increasing incidence of NAFLD and NASH worldwide, the selection of appropriate animal models is important to clarify aspects of pathogenesis and progression in this field.
肥胖、糖尿病、胰岛素抵抗、久坐不动的生活方式和西方饮食是导致非酒精性脂肪性肝病（NAFLD）的关键因素，NAFLD 是发达国家最常见的肝脏疾病之一。在许多情况下，NAFLD 进一步发展为非酒精性脂肪性肝炎（NASH）、纤维化、肝硬化和肝细胞癌。肝脂肪毒性和非肝脏因素，如脂肪组织炎症和胃肠道失衡，与 NAFLD 的演变有关。如今，脂肪组织炎症的程度被证明与 NAFLD 的严重程度直接相关。摄入更高的热量越来越多地被认为是代谢炎症的燃料，不仅与肥胖相关疾病有关，也与 NAFLD 有关。然而，NAFLD 的多种病因是导致 NAFLD 进展为 NASH 的机制仍未被充分理解的原因。在这篇综述中，我们探讨了食物摄入调节肽在 NAFLD 和 NASH 小鼠模型中的作用。瘦素是一种厌食肽，参与肝脏代谢，对 NAFLD 实验模型有影响。胰高血糖素样肽-1（GLP-1），另一种厌食肽，和 GLP-1 受体激动剂（GLP-1R），是预防 NAFLD 进展为 NASH 的潜在治疗药物。另一方面，饥饿激素 ghrelin 的缺失可防止小鼠年龄相关性肝脂肪变性。由于全球范围内 NAFLD 和 NASH 的发病率不断上升，选择合适的动物模型对于阐明该领域发病机制和进展非常重要。
