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07.03.2018 | Original Contribution

Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague–Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression

verfasst von: Gemma Sangüesa, José Carlos Montañés, Miguel Baena, Rosa María Sánchez, Núria Roglans, Marta Alegret, Juan Carlos Laguna

Erschienen in: European Journal of Nutrition | Ausgabe 3/2019

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Abstract

Purpose

Sugar-sweetened beverage intake is a risk factor for insulin resistance, dyslipidemia, fatty liver, and steatohepatitis (NASH). Sub-chronic supplementation of liquid fructose, but not glucose, in female rats increases liver and plasma triglycerides without inflammation. We hypothesized that chronic supplementation of fructose would cause NASH and liver insulin resistance.

Methods

We supplemented female Sprague–Dawley rats with water or either fructose or glucose 10% w/v solutions under isocaloric conditions for 7 months. At the end, plasma analytes, insulin, and adiponectin were determined, as well as liver triglyceride content and the expression of key genes controlling inflammation, fatty acid synthesis and oxidation, endoplasmic reticulum stress, and plasma VLDL clearance, by biochemical and histological methods.

Results

Although sugar-supplemented rats increased their energy intake by 50–60%, we found no manifestation of liver steatosis, fibrosis or necrosis, unchanged plasma or tissue markers of inflammation or fibrosis, and reduced liver expression of gluconeogenic enzymes, despite both sugars increased fatty acid synthesis, mTORC1, and IRE1 activity, while decreasing fatty acid oxidation and PPARα activity. Only fructose-supplemented rats were hypertriglyceridemic, showing a reduced expression of VLDL receptor and lipoprotein lipase in skeletal muscle and vWAT. Glucose-supplemented rats showed increased adiponectinemia, which would explain the different metabolic outcomes of the two sugars.

Conclusions

Chronic liquid simple sugar supplementation, as the sole risk factor, is not enough for female rats to develop NASH and increased liver gluconeogenesis. Nevertheless, under isocaloric conditions, only fructose induced hypertriglyceridemia, thus confirming that also the type of nutrient matters in the development of metabolic diseases.

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Titel: Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague–Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression
verfasst von: Gemma Sangüesa
José Carlos Montañés
Miguel Baena
Rosa María Sánchez
Núria Roglans
Marta Alegret
Juan Carlos Laguna
Publikationsdatum: 07.03.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 3/2019
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-018-1654-9

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