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- Title
Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague-Dawley rats.
- Authors
Jensen, Victoria Svop; Hvid, Henning; Damgaard, Jesper; Nygaard, Helle; Ingvorsen, Camilla; Wulff, Erik Max; Lykkesfeldt, Jens; Fledelius, Christian
- Abstract
Background: 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 efects of a high-fat diet, a high-fructose diet and a combination diet with added cholesterol on the development of NAFLD in rats. Methods: 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. Results: After 16 weeks, liver histology revealed extensive steatosis and infammation in both NASH- and HFD-fed rats, while hepatic changes in HFr-rats were much more subtle. These fndings were corroborated by signifcantly 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 infammation was confrmed 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 infltration (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. Conclusion: These fndings show that dietary fat and cholesterol are the primary drivers of NAFLD development and progression in rats, while fructose mostly exerts its efect on the circulating lipid pool.
- Subjects
DIETARY supplements; FATTY liver; THERAPEUTICS; FRUCTOSE content of food; ASPARTATE aminotransferase; RANDOMIZED controlled trials; ANIMAL models in research
- Publication
Diabetology & Metabolic Syndrome, 2018, Vol 10, p1
- ISSN
1758-5996
- Publication type
Article
- DOI
10.1186/s13098-018-0307-8