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

Research output: Contribution to journalArticle

2 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

Fingerprint

CD4-Positive T-Lymphocytes
Anti-Idiotypic Antibodies
Glucose
Cytokines
T-Lymphocytes
Lipids
Glucose Intolerance
Hyperlipidemias
Lipid Metabolism
Insulin Resistance
Obesity
Liraglutide
Glucagon-Like Peptide-1 Receptor
Liver
Serum

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

GLP-1 receptor agonist, liraglutide, ameliorates hepatosteatosis induced by anti-CD3 antibody in female mice. / Itoh, Arata; Irie, Junichiro; Tagawa, Hirotsune; Kusumoto, Yukie; Kato, Mari; Kobayashi, Nana; Tanaka, Kumiko; Kikuchi, Rieko; Fujita, Masataka; Nakajima, Yuya; Wu, Yuehong; Yamada, Satoru; Kawai, Toshihide; Ridgway, William M.; Itoh, Hiroshi.

In: Journal of Diabetes and its Complications, 2017.

Research output: Contribution to journalArticle

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, WM & Itoh, H 2017, '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
Itoh, Arata ; Irie, Junichiro ; Tagawa, Hirotsune ; Kusumoto, Yukie ; Kato, Mari ; Kobayashi, Nana ; Tanaka, Kumiko ; Kikuchi, Rieko ; Fujita, Masataka ; Nakajima, Yuya ; Wu, Yuehong ; Yamada, Satoru ; Kawai, Toshihide ; Ridgway, William M. ; Itoh, Hiroshi. / GLP-1 receptor agonist, liraglutide, ameliorates hepatosteatosis induced by anti-CD3 antibody in female mice. In: Journal of Diabetes and its Complications. 2017.
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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 na{\"i}ve 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.",
keywords = "CD4-positive T lymphocyte, Glucagon-like peptide-1, Glucose intolerance, Hepatosteatosis, Insulin resistance",
author = "Arata Itoh and Junichiro Irie and Hirotsune Tagawa and Yukie Kusumoto and Mari Kato and Nana Kobayashi and Kumiko Tanaka and Rieko Kikuchi and Masataka Fujita and Yuya Nakajima and Yuehong Wu and Satoru Yamada and Toshihide Kawai and Ridgway, {William M.} and Hiroshi Itoh",
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T1 - GLP-1 receptor agonist, liraglutide, ameliorates hepatosteatosis induced by anti-CD3 antibody in female mice

AU - Itoh, Arata

AU - Irie, Junichiro

AU - Tagawa, Hirotsune

AU - Kusumoto, Yukie

AU - Kato, Mari

AU - Kobayashi, Nana

AU - Tanaka, Kumiko

AU - Kikuchi, Rieko

AU - Fujita, Masataka

AU - Nakajima, Yuya

AU - Wu, Yuehong

AU - Yamada, Satoru

AU - Kawai, Toshihide

AU - Ridgway, William M.

AU - Itoh, Hiroshi

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - CD4-positive T lymphocyte

KW - Glucagon-like peptide-1

KW - Glucose intolerance

KW - Hepatosteatosis

KW - Insulin resistance

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DO - 10.1016/j.jdiacomp.2017.05.013

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JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

SN - 1056-8727

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