Overweight and structural alterations of the liver in female rats fed a high-fat diet: a stereological and histological study

Abstract

Background/aims: The aim of the present study was to investigate the effects of a fatty diet on body weight and liver morphometry in rats via modern stereological methods accompanied by a histological evaluation.

Methods: Eight female "Sprague Dawley" rats were fed a diet constituted highly of fat (30%) for 3 months (the HFD group). Eight control rats were maintained with a standard rat chow. The naso-anal length and body weight of the animals were measured periodically to calculate body mass index. After 3 months, whole livers from the rats were removed, and the volume of each fresh liver was estimated using the water immersion method. After the histological procedure, the volume of paraffin-embedded livers was also estimated using the "Cavalieri" method. Additionally, volumes of the sinusoids and parenchyma were separately estimated with "Cavalieri" method. The mean numerical density, mean nuclear height, and total number of hepatocytes were calculated using the physical disector method. Liver sections were also examined at light and electron microscopic levels.

Results: The body mass indexs of the animals in the control and HFD groups were 4.536+/-0.221 kg/m2 and 5.581+/-0.42 kg/m2, respectively (p<0.01, Mann-Whitney U test). The mean liver volumes (LVs) measured with water immersion method in the control and HFD groups were 10.51 ml and 11.8 ml, respectively. LVs estimated with "Cavalieri" method were 9.98 ml in the control group and 11.095 ml in the HFD group. The differences in LVs between groups were statistically significant when estimated with both methods, indicating that the LV of the HFD group is higher than that of the control group (p<0.05, Mann-Whitney U test). There was no significant difference between LVs estimated via the two different methods in each group (p>0.05, Wilcoxon test). The volume of sinusoids was increased in the HFD group, but the volume of parenchyma was decreased (p<0.05, Mann-Whitney U test). The mean numerical density, mean nuclear height, and total number of hepatocytes were significantly decreased in the HFD group (p<0.05, Mann-Whitney U test). However, the numerical density and total number of binucleated hepatocytes were significantly higher in the HFD group compared with the control group (p<0.05, Mann-Whitney U test). Light and electron microscopic investigations of the HFD group showed a prominent sinusoidal dilatation, microvesicular steatosis, and an increase in connective tissue in the livers and highly dilated smooth endoplasmic reticulum, irregular mitochondria and microvilli and necrosis in the hepatocytes.

Conclusions: We have shown that a fatty diet in rats causes obesity and may lead to morphological alterations in the liver such as hepatomegaly accompanied by histopathological changes.