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Non-alcoholic fatty liver disease (NAFLD): a tale of fat and sugar?


The global diffusion of the so-called Western diet, which is enriched in fat and carbohydrates, such as fructose, has been proposed to be an underlying cause of the increased prevalence of metabolic conditions, including non-alcoholic fatty liver disease (NAFLD). This Smart Card summarizes the main metabolic and hepatic histological features of rodent models fed with diets combining high fat and fructose.


Non-alcoholic fatty liver disease (NAFLD), a condition regarded as the hepatic manifestation of the metabolic syndrome, currently represents the most common cause of chronic liver disease [1]. The condition ranges from simple hepatic fat accumulation (steatosis) to non-alcoholic steatohepatitis, where fat is accompanied by hepatocyte injury, and necroinflammation. This condition poses an increased risk of cirrhosis and hepatocellular carcinoma [1]. The dramatic increase in prevalence of obesity, metabolic syndrome, and NAFLD has been linked to the global diffusion of the Western diet, characterized by excess caloric intake due to increased consumption of processed food and beverages, coupled with a more sedentary lifestyle [2, 3]. This has led to a significant increase in sucrose and high-fructose corn syrup consumption, both of which contain similar amounts of glucose and fructose [4]. In the USA, for example, fructose consumption has more than doubled in the last three decades [3]. Excessive fructose consumption has been linked to an increased prevalence of metabolic diseases and growing evidence suggests that it may also contribute to the development and severity of NAFLD by exacerbating fat deposition, inflammation, and, possibly fibrosis [5]. Mechanistically, fructose may contribute to NAFLD by promoting de-novo lipogenesis, insulin resistance, oxidative stress, bacterial overgrowth, and inflammation [37]. The mechanisms responsible for transition to non-alcoholic steatohepatitis are still not completely understood, in part because of the scarcity of animal models that can fully replicate both the histological and metabolic features of human non-alcoholic steatohepatitis [8]. As fructose is likely to act as a dietary ‘second hit’ [5], effort has recently been put into developing novel experimental models to recapitulate the Western diet by combining high-fat or high-energy diets and fructose. The aim of this Smart Card is to provide a synthetic and exhaustive source for rapid consultation of the currently proposed rodent models of diets combining high fat and fructose, summarizing the metabolic and hepatic consequences of such combinations (Table 1).

Table 1 Metabolic and hepatic features of rodent models fed with diets combining high fat and fructose



Glucose tolerance test: area under the curve


Homeostasis model of assessment - insulin resistance


Non-alcoholic fatty liver disease


Weight by volume.


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Correspondence to Lisa Longato.

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Longato, L. Non-alcoholic fatty liver disease (NAFLD): a tale of fat and sugar?. Fibrogenesis Tissue Repair 6, 14 (2013).

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