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Treatment with alpha‐galactosylceramide protects mice from early onset of nonalcoholic steatohepatitis: Role of intestinal barrier function
Author(s) -
Engstler Anna Janina,
Sellmann Cathrin,
Jin Cheng Jun,
Brandt Annette,
Herz Kathleen,
Priebs Josephine,
Bergheim Ina
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600985
Subject(s) - nonalcoholic steatohepatitis , barrier function , alpha (finance) , steatohepatitis , medicine , biology , nonalcoholic fatty liver disease , microbiology and biotechnology , disease , fatty liver , construct validity , nursing , patient satisfaction
Scope The role of invariant natural killer T cells in the development of nonalcoholic 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 nonalcoholic 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 wk while being treated three times weekly with αGalCer (2 μg intraperitoneal) 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.