[Effect of high-fat diet, rosiglitazone on lipid profile, insulin resistance and liver steatosis development].

UNLABELLED: The effect of diet on the development of liver steatosis is a rarely analyzed problem. No effective methods of treatment of nonalcoholic steatohepatitis have been developed, either. The aim of the study was to assess the effect of high-fat diet and rosiglitazone administration on (1) lipid parameters in the serum, (2) insulin resistance and (3) development of liver steatosis.

MATERIALS AND METHODS: The material comprised 60 adult male Wistar rats. The animals were divided into 5 main groups. The first three groups (AT, AR and AL) were fed with high-fat diets (63% energy from fats, 23% from carbohydrates), the animals in the remaining two ones (KH and KL) received low-fat diet (10% energy from fats, 57% from carbohydrates). Rats from the AL and KL groups received rosiglitazone (10 micromol/ kg b.w.) through a gastric tube. After 9 weeks, the experiment was terminated in groups AT, AL, KL whereas in the AR group high-fat diet was replaced with low-fat diet after 9 weeks and the experiment was terminated after further 7 weeks.

RESULTS: The highest rates of liver steatosis were observed in groups receiving high-fat diet, both in the group where rosiglitazone was administered (10/12; 83.3%) and in the group fed with high-fat diet only (8/12; 66.6%). In group AR, as well as in both KH and KL groups no cases of liver steatosis were observed. Group AT demonstrated the highest mean levels of total cholesterol in the serum in comparison with AL (p<0.01), AR (p<0.001), KH (p<0.00001) and KL (p<0.00001). Simultaneously, significantly higher triglyceride level was found in group AT as compared with AL (p<0.001) and KL (p<0.01). In the AL. vs. AT group, besides lower glucose level, lower concentrations of insulin (p<0.0001), peptide C (p<0.000001), as well as lower insulin secretion index (p<0.0001) and insulin resistance (HOMA) (p<0.001) were also observed. A comparison of groups AT and KH revealed a significant increase of mean glucose level (p<0.0001) and peptide C (p<0.05) in group KH in comparison with AT.

CONCLUSIONS: 1. High-fat diet promotes the development of unfavorable lipid profile changes (hypercholesterolemia, hypertriglyceridemia), insulin resistance, as well as the development of liver steatosis. 2. Rosiglitazone exerts a favorable effect on both lipid profile and regulation of insulin secretion, but it does not reduce the risk of liver steatosis.