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Diet-induced dyslipidemia leads to nonalcoholic fatty liver disease and oxidative stress in guinea pigs

Published:October 13, 2015DOI:https://doi.org/10.1016/j.trsl.2015.10.001
      Chronic dyslipidemia imposed by a high-fat and high-caloric dietary regime leads to debilitating disorders such as obesity, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. As disease rates surge, so does the need for high validity animal models to effectively study the causal relationship between diet and disease progression. The dyslipidemic guinea pig displays a high similarity with the human lipoprotein profile and may in this aspect be superior to other rodent models. This study investigated the effects of 2 long-term Westernized diets (0.35% cholesterol, 18.5% vegetable oil and either 15% or 20% sucrose) compared with isocaloric standard chow in adult guinea pigs. Biochemical markers confirmed dyslipidemia in agreement with dietary regimens; however, both high-fat groups displayed a decreased tissue fat percentage compared with controls. Macroscopic appearance, histopathologic evaluation, and plasma markers of liver function confirmed NAFLD in high-fat groups, supported by liver redox imbalance and markers suggesting hepatic endothelial dysfunction. Plasma markers indicated endothelial dysfunction in response to a high-fat diet, although atherosclerotic lesions were not evident. Evaluation of glucose tolerance showed no indication of insulin resistance. The 5% increase in sucrose between the 2 high-fat diets did not lead to significant differences between groups. In conclusion, we find the dyslipidemic guinea pig to be a valid model of diet imposed dyslipidemia, particularly with regards to hepatic steatosis and endothelial dysfunction. Furthermore, the absence of obesity supports the present study setup as targeting NAFLD in nonobese individuals.

      Abbreviations:

      ADMA (asymmetric dimethylarginine), ALP (alkaline phosphatase), ALT (alanine aminotransferase), AST (aspartate aminotransferase), BH2 (dihydrobiopterin), BH4 (tetrahydrobiopterin), BW (body weight), CTRL (isocaloric control standard chow diet), DEXA (dual-energy x-ray absorptiometry), eNOS (endothelial nitric oxide synthase), GSH (glutathione), GSSG (oxidized glutathione), H&E (Mayer's hematoxylin and eosin), HDL (high-density lipoprotein), HF (high fat + 15% sucrose), HFS (high fat + 20% sucrose), HPLC (high-performance liquid chromatography), L-Arg (L-arginine), LDL (low-density lipoprotein), MDA (malondialdehyde), NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), NO (nitric oxide), OGTT (oral glucose tolerance test), Ox-LDL (oxidized low-density lipoprotein), SOD (superoxide dismutase), TC (total cholesterol), TG (triglyceride), VitC (vitamin C), VLDL (very low-density lipoprotein)
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