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C57BL\/6J\u2010Lean mice were utilized as the control group. Plasma parameters, liver histopathology, and hepatic status were measured. For the in vitro study, macrophage\u2010derived RAW264.7 cells were cultured with AM251 or CB1 small interfering RNA (siRNA) before challenge with arachidonyl\u20102\u2032\u2010chloroethylamide (ACEA) or a high concentration of fatty acids (HFFAs). The <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice exhibited an increase in CB1 levels, lipid droplet accumulation, mitogen\u2010activated protein kinase\u2010related inflammatory responses, and macrophage and neutrophil infiltration in the liver tissues. Flow cytometry analysis revealed an elevation in macrophages and T helper cells, plus a decrease in natural killer T cells and regulatory T cells in the liver tissues of the <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice; treatment with 5\u2009mg\/kg AM251 reversed these changes. Moreover, in vitro experiments revealed that administration of 3.3\u2009\u03bcM AM251 or CB1 siRNA prevented 1\u2009mM HFFA\u2010 and 1\u2009\u03bc\u039c ACEA\u2010induced inflammatory cytokine protein expression in the RAW264.7 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggested that a blockade caused by CB1 reduced obesity\u2010associated NASH progression via correction of immune system dysregulations and elevated inflammatory responses in the liver tissues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.338","type":"journal-article","created":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T09:59:39Z","timestamp":1597485579000},"page":"544-558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cannabinoid receptor type 1 antagonist inhibits progression of obesity\u2010associated nonalcoholic steatohepatitis in a mouse model by remodulating immune system 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