Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague-Dawley rats.

Autor: Jensen VS; 1Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, Denmark.; 2Insulin Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark., Hvid H; 2Insulin Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark., Damgaard J; 2Insulin Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark., Nygaard H; 2Insulin Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark., Ingvorsen C; 3Histology and Imaging, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark., Wulff EM; 4Obesity and Diabetes Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark., Lykkesfeldt J; 1Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, Denmark., Fledelius C; 2Insulin Pharmacology, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Maaloev, Denmark.
Jazyk: angličtina
Zdroj: Diabetology & metabolic syndrome [Diabetol Metab Syndr] 2018 Jan 24; Vol. 10, pp. 4. Date of Electronic Publication: 2018 Jan 24 (Print Publication: 2018).
DOI: 10.1186/s13098-018-0307-8
Abstrakt: 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 effects 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 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.
Conclusion: 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.
Databáze: MEDLINE
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