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Diabetology & Metabolic Syndrome
Published in: Diabetology & Metabolic Syndrome 1/2018

Open Access 01-12-2018 | Research

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

Authors: Victoria Svop Jensen, Henning Hvid, Jesper Damgaard, Helle Nygaard, Camilla Ingvorsen, Erik Max Wulff, Jens Lykkesfeldt, Christian Fledelius

Published in: Diabetology & Metabolic Syndrome | Issue 1/2018

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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 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.
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Metadata
Title
Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague–Dawley rats
Authors
Victoria Svop Jensen
Henning Hvid
Jesper Damgaard
Helle Nygaard
Camilla Ingvorsen
Erik Max Wulff
Jens Lykkesfeldt
Christian Fledelius
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2018
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-018-0307-8

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