Short-Term Intake of a Fructose-, Fat- and Cholesterol-Rich Diet Causes Hepatic Steatosis in Mice: Effect of Antibiotic Treatment
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, A-1090 Vienna, Austria
Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, D-07743 Jena, Germany
Author to whom correspondence should be addressed.
Nutrients 2017, 9(9), 1013; https://doi.org/10.3390/nu9091013
Received: 14 June 2017 / Revised: 31 August 2017 / Accepted: 11 September 2017 / Published: 14 September 2017
(This article belongs to the Special Issue Nutrition and Non-alcoholic Fatty Liver Disease)
Intestinal microbiota and barrier functions seem to play an important role in the development of non-alcoholic fatty liver disease (NAFLD). However, whether these changes are an early event in the development of NAFLD or are primarily associated with later stages of the disease, has not yet been clarified. Using a pair-feeding model, we determined the effects of a short-term intake of a fat-, fructose- and cholesterol-rich diet (FFC) on the development of early hepatic steatosis and markers of intestinal barrier function in mice treated with and without non-resorbable antibiotics (AB). For four days, C57BL/6J mice were either pair-fed a control diet or a FFC diet ± AB (92 mg/kg body weight (BW) polymyxin B and 216 mg/kg BW neomycin). Hepatic steatosis and markers of inflammation, lipidperoxidation and intestinal barrier function were assessed. Lipid accumulation and early signs of inflammation found in the livers of FFC-fed mice were markedly attenuated in FFC + AB-fed animals. In FFC-fed mice the development of NAFLD was associated with a significant loss of tight junction proteins and an induction of matrix metalloproteinase-13 in the upper parts of the small intestine as well as significantly higher portal endotoxin levels and an induction of dependent signaling cascades in the liver. As expected, portal endotoxin levels and the expression of dependent signaling cascades in liver tissue were almost at the level of controls in FFC + AB-fed mice. However, FFC + AB-fed mice were also protected from the loss of zonula occludens-1 and partially of occludin protein in small intestine. Our data suggest that the development of early diet-induced hepatic steatosis in mice at least in part results from alterations of intestinal barrier function.