Treatment with alpha-galactosylceramide protects mice from early onset of non-alcoholic steatohepatitis

Anna Janina Engstler, Cathrin Sellmann, Cheng Jun Jin, Annette Brandt, Kathleen Herz, Josephine Priebs, Ina Bergheim

SCOPE: The role of invariant natural killer T cells in the development of non-alcoholic steatohepatitis (NASH) has not yet been fully understood. Here, the effect of the invariant natural killer T cell activator alpha-galactosylceramide (αGalCer) on the development of non-alcoholic fatty liver disease and intestinal barrier function was assessed in a mouse model of early Western-style diet (WSD)-induced NASH.

METHODS AND RESULTS: Female C57BL/6J mice were either fed a liquid control diet or a liquid fructose-enriched WSD for 6 weeks while being treated 3-times weekly with αGalCer (2 μg i.p.) or vehicle. Indices of liver damage, glucose metabolism and intestinal permeability were measured. Treatment with αGalCer markedly suppressed hepatic fat accumulation and inflammation while not affecting fasting glucose. The protective effects of αGalCer were associated with a protection against the increased translocation of bacterial endotoxins and the decreased protein levels of tight junction proteins occludin and zonula occludens 1 found in vehicle-treated mice while being fed a WSD.

CONCLUSION: Taken together, our data suggest that the protective effects of αGalCer against the development of a diet-induced NASH in mice are associated with a protection against the increased translocation of intestinal bacterial endotoxins associated with the development of NASH. This article is protected by copyright. All rights reserved.

Department für Ernährungswissenschaften
Externe Organisation(en)
Friedrich-Schiller-Universität Jena
Molecular Nutrition & Food Research
Anzahl der Seiten
ÖFOS 2012
303009 Ernährungswissenschaften
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