In humans and animal models, excessive intake of dietary fat, fructose and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD). However, the individual roles of the dietary components remain unclear. To investigate this further, we compared the effects of a high-fat diet, a high-fructose diet and a combination diet with added cholesterol on the development of NAFLD in rats.
Forty male Sprague–Dawley rats were randomized into four groups receiving either a control-diet (Control: 10% fat); a high-fat diet (HFD: 60% fat, 20% carbohydrate), a high-fructose diet [HFr: 10% fat, 70% carbohydrate (mainly fructose)] or a high-fat/high-fructose/high-cholesterol-diet (NASH: 40% fat, 40% carbohydrate (mainly fructose), 2% cholesterol) for 16 weeks.
After 16 weeks, liver histology revealed extensive steatosis and inflammation in both NASH- and HFD-fed rats, while hepatic changes in HFr-rats were much more subtle. These findings were corroborated by significantly elevated hepatic triglyceride content in both NASH- (p < 0.01) and HFD-fed rats (p < 0.0001), elevated hepatic cholesterol levels in NASH-fed rats (p < 0.0001), but no changes in HFr-fed rats, compared to Control. On the contrary, only HFr-fed rats developed dyslipidemia as characterized by higher levels of plasma triglycerides compared to all other groups (p < 0.0001). Hepatic dysfunction and inflammation was confirmed in HFD-fed rats by elevated levels of hepatic MCP-1 (p < 0.0001), TNF-alpha (p < 0.001) and plasma β-hydroxybutyrate (p < 0.0001), and in NASH-fed rats by elevated levels of hepatic MCP-1 (p < 0.01), increased hepatic macrophage infiltration (p < 0.001), and higher plasma levels of alanine aminotransferase (p < 0.0001) aspartate aminotransferase (p < 0.05), haptoglobin (p < 0.001) and TIMP-1 (p < 0.01) compared to Control.
These findings show that dietary fat and cholesterol are the primary drivers of NAFLD development and progression in rats, while fructose mostly exerts its effect on the circulating lipid pool.
Hojland Ipsen D, Tveden-Nyborg P, Lykkesfeldt J. Normal weight dyslipidemia: is it all about the liver? Obesity (Silver Spring). 2016;24:556–67. CrossRef
Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, et al. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol. 2006;169:846–60. CrossRefPubMedPubMedCentral
Metzinger MN, Miramontes B, Zhou P, Liu Y, Chapman S, Sun L, Sasser TA, Duffield GE, Stack MS, Leevy WM. Correlation of X-ray computed tomography with quantitative nuclear magnetic resonance methods for pre-clinical measurement of adipose and lean tissues in living mice. Sensors (Basel). 2014;14:18526–42. CrossRefPubMedCentral
Ipsen DH, Tveden-Nyborg P, Rolin B, Rakipovski G, Beck M, Mortensen LW, Faerk L, Heegaard PM, Moller P, Lykkesfeldt J. High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs. Nutr Metab (Lond). 2016;13:51. CrossRef
Luo Y, Burrington CM, Graff EC, Zhang J, Judd RL, Suksaranjit P, Kaewpoowat Q, Davenport SK, O’Neill AM, Greene MW. Metabolic phenotype and adipose and liver features in a high-fat western diet-induced mouse model of obesity-linked NAFLD. Am J Physiol Endocrinol Metab. 2016;310:E418–39. CrossRefPubMed
Wouters K, van Gorp PJ, Bieghs V, Gijbels MJ, Duimel H, Lutjohann D, Kerksiek A, van Kruchten R, Maeda N, Staels B, et al. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology. 2008;48:474–86. CrossRefPubMed
Merat S, Sotoudehmanesh R, Nouraie M, Peikan-Heirati M, Sepanlou SG, Malekzadeh R, Sotoudeh M. Sampling error in histopathology findings of nonalcoholic fatty liver disease: a post mortem liver histology study. Arch Iran Med. 2012;15:418–21. PubMed
Safwat GM, Pisano S, D’Amore E, Borioni G, Napolitano M, Kamal AA, Ballanti P, Botham KM, Bravo E. Induction of non-alcoholic fatty liver disease and insulin resistance by feeding a high-fat diet in rats: does coenzyme Q monomethyl ether have a modulatory effect? Nutrition. 2009;25:1157–68. CrossRefPubMed
Lieber CS, Leo MA, Mak KM, Xu Y, Cao Q, Ren C, Ponomarenko A, DeCarli LM. Model of nonalcoholic steatohepatitis. Am J Clin Nutr. 2004;79:502–9. PubMed
- Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague–Dawley rats
Victoria Svop Jensen
Erik Max Wulff
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II