Fatty Liver Promotes Fibrosis In Monkeys Consuming High Fructose

OBJECTIVE: Non-alcoholic 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. We aimed to document a monkey model of fatty liver and fibrosis, which naturally develop cardiometabolic disease pathophysiologies. METHODS: We studied 27 cynomologus monkeys (Macaca fascicularis) fed diets either low or high in simple carbohydrates, supplied as fructose, (CTL and HFr), on low fat, cholesterol-free background. The HFr was consumed for up to 7 years and liver tissue was histologically evaluated for fat and fibrosis extent. RESULTS: 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 to CTL 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. CONCLUSIONS: These data are the first to demonstrate that high carbohydrate diets alone can generate both liver fat and fibrosis and thus allows further study of mechanisms and therapeutic options in this translational animal model.