Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic linked to metabolic disease. The first stage of NAFLD is characterized by lipid accumulation in hepatocytes, but this can progress into non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Western diets, high in fats, sugars and cholesterol are linked to NAFLD development. Murine models are often used to study NAFLD; however, there remains debate on which diet-induced model best mimics both human disease progression and pathogenesis. In this study, we performed a side-by-side comparison of two popular diet models of murine NAFLD/NASH and associated HCC: a high fat diet supplemented with 30% fructose water (HFHF) and a western diet high in cholesterol (WDHC), comparing them to a common grain-based chow diet (GBD). Mice on both experimental diets developed liver steatosis, while WDHC-fed mice had greater levels of hepatic inflammation and fibrosis than HFHF-fed mice. In contrast, HFHF-fed mice were more obese and developed more severe metabolic syndrome, with less pronounced liver disease. Despite these differences, WDHC-fed and HFHF-fed mice had similar tumour burdens in a model of diet-potentiated liver cancer. Response to diet and resulting phenotypes were generally similar between sexes, albeit delayed in females. This study shows that modest differences in diet can significantly uncouple glucose homeostasis and liver damage. In conclusion, long-term feeding of either HFHF or WDHC are reliable methods to induce NASH and diet-potentiated liver cancer in mice of both sexes; however, the choice of diet involves a trade-off between severity of metabolic syndrome and liver damage.

中文翻译：

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非酒精性脂肪肝的两种饮食小鼠模型引起的代谢和肝脏病理生物学差异。

非酒精性脂肪肝疾病（NAFLD）是一种与代谢疾病有关的流行病。NAFLD的第一阶段的特征是脂质在肝细胞中蓄积，但这会发展为非酒精性脂肪性肝炎（NASH），肝硬化和肝细胞癌（HCC）。富含脂肪，糖和胆固醇的西方饮食与NAFLD的发展有关。鼠模型通常用于研究NAFLD。然而，关于哪种饮食诱导模型最能模仿人类疾病的进展和发病机理仍存在争议。在这项研究中，我们对两种流行的鼠类NAFLD / NASH和相关HCC饮食模型进行了并排比较：高脂饮食和30％果糖水（HFHF）补充了高胆固醇饮食（WDHC） ，将它们与普通的谷类食物（GBD）进行比较。两种实验饮食的小鼠均发生肝脂肪变性，而WDHC喂养的小鼠的肝脏炎症和纤维化水平高于HFHF喂养的小鼠。相比之下，HFHF喂养的小鼠更肥胖，发展为更严重的代谢综合征，肝脏疾病较少。尽管存在这些差异，但在饮食增强型肝癌模型中，由WDHC喂养和HFHF喂养的小鼠的肿瘤负荷相似。性别之间对饮食和产生的表型的反应一般相似，尽管女性延迟。这项研究表明，饮食上的适度差异可以使葡萄糖稳态和肝脏损害脱钩。总之，长期饲喂HFHF或WDHC是诱导性别和NASH和饮食增强的肝癌的可靠方法。然而，