Aims Hepatosteatosis is mainly induced by obesity and metabolic disorders, but various medications also induce hepatosteatosis. The administration of anti-CD3 antibody was shown to induce hepatosteatosis, but changes in lipid and glucose metabolism remain unclear. We investigated the mechanism of hepatosteatosis induced by anti-CD3 antibody and the effects of glucagon-like peptide-1 (GLP-1) receptor agonist that was recently shown to affect immune function in metabolic disorders. Methods Anti-CD3 antibody was administered to female BALB/c and C.B-17- scid mice with or without reconstitution by naive CD4-positive splenocytes. Hepatic lipid content, serum lipid profile and glucose tolerance were evaluated. Splenic CD4-positive T lymphocytes were stimulated with the GLP-1R agonist, liraglutide, and cytokine production was measured. The effect of liraglutide on metabolic parameters in vivo was investigated in a T-cell activation-induced hepatosteatosis model. Results The administration of anti-CD3 antibody induced hepatosteatosis, hyperlipidemia, and glucose intolerance. C.B-17- scid mice reconstituted with CD4-positive T lymphocytes developed hepatosteatosis induced by anti-CD3 antibody. Liraglutide suppressed CD4-positive T lymphocyte cytokine expression in vitro and in vivo , and improved hepatosteatosis, glucose tolerance, and insulin sensitivity. Conclusions Liraglutide suppressed the activation of CD4-positive T lymphocytes, and improved hepatosteatosis and metabolic disorders induced by T-cell activation in female mice.
