While fat and cholesterol both seem to contribute to the development of NAFLD, previous studies in rats have shown that also high levels of dietary fructose are capable of inducing hepatic steatosis, inflammation and increase oxidative stress markers within a relatively short time-span of only 2–5 weeks [32–34]. These are in contrast to our findings with the HFr-diet, which only induced subtle changes in the liver. While steatosis was observed histologically in some animals in the HFr-group the condition was not confirmed by increased levels of liver TG at the week 16 time point. The apparent discrepancy between histological and biochemical analyses within the HFr-group could result from sampling variation, a problem also commonly encountered in biopsy-guided diagnosis of human NAFLD/NASH . Biochemical analyses of hepatic TG-content was performed on liver tissue sampled from the left lateral lobe and histologic evaluation of livers in the HFr-group (performed on both left lateral, right medial and the caudate lobe) did in fact, in some animals, show specific lobes to be more severely affected than others, indicating that steatosis, at least in rats fed fructose-enriched diets, may not be homogenously distributed throughout the liver. Further studies, confirming the heterogeneously distributed steatosis would be interesting in terms of evaluating and comparing histology, biochemistry and imaging of the liver in rodent models of NAFLD/NASH.