Experimental model of high-fat diet is useful to evaluate the aggravation of liver damage associated with comorbidities





Fatty liver; Animal models; Diet; Non-alcoholic fatty liver disease.


Objetive: Develop a high-fat diet (HFD) model that standing alone did not develop the Non-alcoholic fatty liver disease (NAFLD), allowing one to study the association of comorbidities with the high-fat diet model. Material and methods: The rats were divided into 2 groups: standard diet and high-fat diet, each group with 8 animals. The rats were submitted to the analysis of the following parameters in hepatic tissue: dosage of malondialdehyde (MDA), glutathione (GSH) and myeloperoxidase activity (MPO). Liver samples were also assessed histopathologically for serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), alkaline phosphatase (FAL), uric acid and total cholesterol (TC), calcium (CA), urea and HDL. Results: The results showed that there was a significant difference in MDA, GSH, total cholesterol (CT), ALT, ALB, uric acid (AU), calcium (CA) and HDL. The histopathological evaluation presented a low score, insufficient for the classification of NAFLD. Conclusion: This study demonstrated that the high-fat diet model did not cause NAFLD. This finding allows one to use the high-fat diet characterized in this study to investigate the possible hepatic alterations caused by other comorbidities.


Brunt, E. M. & Tiniakos, D. G. (2009). Fatty Liver Disease. In Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas (1087-1114). Elsevier Inc. https://doi.org/10.1016/B978-141604059-0.50044-8.

Buettner, R. et al. (2006). Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol; 6(3), 485– 501. https:// doi.org/10.1677/jme.1.01909.

Chalasani, N. et al. (2012). The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases. Hepatology, (55). https:// doi.org/ 10.1002/hep.25762.

Chaves, L. S., Nicolau, L. A. & Silva, R. O. et al. (2013). Antiinflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction extracted from the marine red alga e Gracilaria caudata. Immunopharmacol Immunotoxicol, 35, 93-100. https://doi.org/ 10.3109/08923973.2012.707211.

Della, P. G. et al. (2017). Isocaloric Dietary Changes and Non-Alcoholic Fatty Liver Disease in High Cardiometabolic Risk Individuals. Nutrients, 26(9), 1065- 10. https:// doi.org/ 10.3390/nu9101065.

Dou et al. (2018). Glutathione disulfide sensitizes hepatocytes to TNFα-mediated cytotoxicity via IKK-β S-glutathionylation: a potential mechanism underlying non-alcoholic fatty liver disease. Experimental & Molecular Medicine, 50(7). https://doi.org/10.1038/s12276-017-0013-x.

Eshraghian, A. (2017). Bone metabolism in non-alcoholic fatty liver disease: vitamin d status and bone mineral density. Minerva endocrinológica, June;42(2), 164-72. https://doi.org/10.23736/S0391-1977.16.02587-6.

Ghibaudi, L. et al. (2002). Fat intake affects adiposity, comorbidity factors, and energy metabolism of sprague-dawley rats. Obes Res., 10, 956–963. https://doi.org/10.3390/nu9101072.

Herck, V. M., Vonghia, L. & Francque, S. M. (2017) Animal Models of Nonalcoholic Fatty Liver Disease - A Starter’s Guide. Nutrients, 9(10), 1072. https://doi.org/10.1038/oby.2002.130.

Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444:860-7. https://doi.org/10.1038/nature05485.

Hu, Xiao-Yu et al. (2018). Risk Factors and Biomarkers of Non-Alcoholic Fatty Liver Disease: An Observational Cross-Sectional Population Survey. BMJ Open, 12. https://doi.org/ 10.1136/bmjopen-2017-019974.

Ibrahim, S.H., Hirsova, P., Malhi, H. & Gores, G.J. (2016) Animal models of nonalcoholic steatohepatitis: Eat, delete, and inflame. Dig. Dis. Sci., 61, 1325–1336. https://doi.org/ 10.1007/s10620-015-3977-1.

Kanuri, G. & Bergheim, I. (2013). In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD). Int J Mol Sci. 14:11963–80. https://doi.org/ 10.3390/ijms140611963.

Keefe, E. B. (2001). Liver transplantation: current status and novel approaches to liver. Gastroenterology, 120(3), 749-62. https://doi.org/10.1053/gast.2001.22583.

Khan, et al. (2015). Carbon tetrachloride-induced lipid peroxidation and hyperglycemia in rat: A novel study, Toxicol. Ind. Health, 31, 546–553. https://doi.org/ 10.1177/0748233713475503.

Krishan, S. (2016). Correlation between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia in type 2 diabetes. Diab Met Syndr: Clin Res Ver, 10, 77-81. https://doi.org/ 10.1016/j.dsx.2016.01.034.

Kleiner, D. E., Brunt, E. M. & Van Natta, M. et al. (2005). Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology; 41, 1313-21. https://doi.org/ 10.1002/hep.20701

Kulkarni, N. M et al. (2014). A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation. Pharmaceutical Biology, 53(8), 1110–1117. https://doi.org/ 10.3109/13880209.2014.960944.

Lau, J. K. C. & Zhang, X. Y. U. J. (2017). Animal models of non‐alcoholic fatty liver disease: current perspectives and recent advances. The Journal of Pathology, 241(1), 36-44. https://doi.org/ 10.1002/path.4829.

Lozano, et al. (2016). High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutrition & Metabolism, 13(15). https://doi.org/ 10.1186/s12986-016-0074-1.

Ly, F. et al. (2017). Deficiency promotes nonalcoholic steatohepatitis via regulation of hepatic oxidative stress. Biochem. Biophys. Res. Commun,, 486, 264–269. https://doi.org/ 10.1016/j.bbrc.2017.03.023.

Mcdonald, S. D. et al. (2011). “Adverse metabolic effects of a hypercaloric, high-fat diet in rodents precede observable changes in body weight”. Nutrition Research, 31, 707–71. https://doi.org/ 10.1016/j.nutres.2011.08.009.

Mikolasevic, I. et al. (2014). Nonalcoholic fatty liver disease: a new factor that interplays between inflammation, malnutrition, and atherosclerosis in elderly hemodialysis patients. Clin. Interv. Aging. 9, 1295–1303. https://doi.org/ 10.2147/CIA.S65382.

Neuman, M. G.; Cohen, L. B. & Nanau, R. M. (2014).Biomarkers in nonalcoholic fatty liver disease. Canadian Journal of Gastroenterology & Hepatology, 28(11), 607-618.

Noureddin, M. D. & Rohit, L. (2012). Nonalcoholic fatty liver disease: indications for liver biopsy and noninvasive biomarkers mazen. Clin. Liver Dis., 1, 25–38. https://doi.org/10.1002/cld.65.

Polimeni, L, et al. (2015). Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J Hepatol., 7(10), 1325–36. https://doi.org/ 10.4254/wjh.v7.i10.1325.

Sattar, N., Forrest, E. & Preiss, D. (2014). Non-alcoholic fatty liver disease. BMJ, 349, 4596. https://doi.org/ 10.1136/bmj.g4596.

Sedlak, J. & Lindsay, R.H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 24, 192–205.

Takahashi, Y., Soejima, Y. & Fukusato, T. (2012) Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol, 18:2300–8. https://doi.org/ 10.3748/wjg.v18.i19.2300.

Takaki, A.; Kawai, D. & Yamamoto, K. (2013). Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int. J. Mol. Sci., 14, 20704 –20728. https://doi.org/ 10.3390/ijms141020704.

Tandra, S.; Yeh, M. M. & Brunt, E. M. et al. (2011). Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease. J Hepatol., 55, 654–659. https://doi.org/ 10.1016/j.jhep.2010.11.021.

Tannaz, E., Puneeta, T. & Maitreyi R. (2017). Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease. Nutrients, 9, 800. https://doi.org/ 10.3390/nu9080800.

Tetri L. H. et al. (2008). Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalente. Am J Physiol Gastrointest Liver Physiol, 295, G987-G995. https://doi.org/ 10.1152/ajpgi.90272.2008.

Toshimitsu, K. et al. (2007). Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition, 23, 46-52. https://doi.org/ 10.1016/j.nut.2006.09.004.

Thulin, P. et al. (2008). PPARalpha regulates the hepatotoxic biomarker alanine aminotransferase (ALT1) gene expression in human hepatocytes. Toxicol Appl Pharmacol, 231, 1–9. https://doi.org/ 10.1016/j.taap.2008.03.007.

Uchiyama, M., & Mihara M. (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Ana Biochem, 86, 271–278. https://doi.org/10.1016/0003-2697(78)90342-1.

Wu, L., Li, T. & Wen, Y.Q. Li. (2007). Protective effects of echinacoside on carbontetrachloride-induced hepatotoxicity in rats, Toxicol., 232, 50–56. https://doi.org/ 10.1016/j.tox.2006.12.013.

Yesolova Z. et al. (2005). Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic fatty liver disease. Am J Gastroenterol, 2005, 100(4), 850–5. https://doi.org/ 10.1111/j.1572-0241.2005.41500.x.

Yulong, W. U. et al. (2018). Chicory (Cichorium intybus L.) polysaccharides attenuate highfat diet induced non-alcoholic fatty liver disease via AMPK activation. Biomac. https://doi.org/ 10.1016/j.ijbiomac.2018.06.140.



How to Cite

RODRIGUES, A. A. .; ALVES, E. H. P. .; ANDRADE, R. S. B. de .; FRANÇA, L. F. de C. .; PESSOA, L. dos S. .; SILVA, F. R. P. da .; LENARDO, D. D. .; NASCIMENTO, H. M. S. .; CARVALHO, A. dos S. .; SOUSA, F. B. de M. .; MARTINS, V. B. D. .; BARBOSA, A. L. dos R.; MEDEIROS, J.-V. R. .; VASCONCELOS, A. C. C. G. .; VASCONCELOS, D. F. P. . Experimental model of high-fat diet is useful to evaluate the aggravation of liver damage associated with comorbidities. Research, Society and Development, [S. l.], v. 10, n. 3, p. e1310313012, 2021. DOI: 10.33448/rsd-v10i3.13012. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/13012. Acesso em: 12 apr. 2021.



Health Sciences