Cydylo Michael A, Davis Ashley T, Kavanagh Kylie
Wake Forest School of Medicine Department of Pathology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
Obesity (Silver Spring). 2017 Feb;25(2):290-293. doi: 10.1002/oby.21720.
Nonalcoholic fatty liver diseases (NAFLD) are related to development of liver fibrosis which currently has few therapeutic options. Rodent models of NAFLD inadequately model the fibrotic aspects of the disease and fail to demonstrate the spectrum of cardiometabolic diseases without genetic manipulation. This study aimed to document a monkey model of fatty liver and fibrosis, which naturally develop cardiometabolic disease pathophysiologies.
Twenty-seven cynomolgus monkeys (Macaca fascicularis) fed diets either low or high in simple carbohydrates, supplied as fructose [control and high-fructose diet (HRr)], on low-fat, cholesterol-free background were studied. The HFr was consumed for up to 7 years, and liver tissue was histologically evaluated for fat and fibrosis extent.
The HFr diet increased steatosis, and its extent was related to duration of fructose exposure. Lipid droplet size also increased with HFr duration; however, compared with control, the lipid droplets were smaller on average. Fibrosis extent was significantly greater with fructose feeding and was predicted by fructose exposure, extent of fatty liver, and age.
These data are the first to demonstrate that high-carbohydrate diets alone can generate both liver fat and fibrosis and thus allow further study of mechanisms and therapeutic options in the translational animal model.
非酒精性脂肪性肝病（NAFLD）与肝纤维化的发展相关，而目前针对肝纤维化的治疗选择有限。NAFLD的啮齿动物模型无法充分模拟该疾病的纤维化特征，并且在未经基因操作的情况下无法展现出心脏代谢疾病的全貌。本研究旨在记录一种自然发生心脏代谢疾病病理生理学的脂肪肝和肝纤维化猴模型。
对27只食蟹猴（猕猴属）进行研究，它们在低脂、无胆固醇的饮食背景下，分别喂食简单碳水化合物含量低或高的饮食，高碳水化合物饮食以果糖形式提供[对照组和高果糖饮食组（HFr）]。高果糖饮食持续摄入长达7年，对肝脏组织进行脂肪和纤维化程度的组织学评估。
高果糖饮食增加了脂肪变性，其程度与果糖暴露持续时间相关。脂滴大小也随高果糖饮食持续时间增加；然而，与对照组相比，脂滴平均较小。果糖喂养组的纤维化程度显著更高，且可通过果糖暴露、脂肪肝程度和年龄进行预测。
这些数据首次表明，仅高碳水化合物饮食就能导致肝脏脂肪和纤维化，从而为在转化动物模型中进一步研究机制和治疗选择提供了可能。
