GLP-1 receptor agonist, liraglutide, ameliorates hepatosteatosis induced by anti-CD3 antibody in female mice

Arata Itoh, Junichiro Irie, Hirotsune Tagawa, Yukie Kusumoto, Mari Kato, Nana Kobayashi, Kumiko Tanaka, Rieko Kikuchi, Masataka Fujita, Yuya Nakajima, Yuehong Wu, Satoru Yamada, Toshihide Kawai, William M. Ridgway, Hiroshi Itoh

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3 Citations (Scopus)

Abstract

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 naïve 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.

Original languageEnglish
JournalJournal of Diabetes and its Complications
DOIs
Publication statusAccepted/In press - 2017

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Keywords

  • CD4-positive T lymphocyte
  • Glucagon-like peptide-1
  • Glucose intolerance
  • Hepatosteatosis
  • Insulin resistance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Itoh, A., Irie, J., Tagawa, H., Kusumoto, Y., Kato, M., Kobayashi, N., Tanaka, K., Kikuchi, R., Fujita, M., Nakajima, Y., Wu, Y., Yamada, S., Kawai, T., Ridgway, W. M., & Itoh, H. (Accepted/In press). GLP-1 receptor agonist, liraglutide, ameliorates hepatosteatosis induced by anti-CD3 antibody in female mice. Journal of Diabetes and its Complications. https://doi.org/10.1016/j.jdiacomp.2017.05.013