GLP-1 receptor agonist, liraglutide, ameliorates hepatosteatosis induced by anti-CD3 antibody in female mice
| Autor: | Rieko Kikuchi, Mari Kato, Hirotsune Tagawa, Hiroshi Itoh, Nana Kobayashi, Toshihide Kawai, Satoru Yamada, William M. Ridgway, Yuya Nakajima, Yuehong Wu, Junichiro Irie, Masataka Fujita, Arata Itoh, Kumiko Tanaka, Yukie Kusumoto |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist CD4-Positive T-Lymphocytes medicine.medical_specialty CD3 Complex medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Mice SCID Lymphocyte Activation Antibodies Glucagon-Like Peptide-1 Receptor 03 medical and health sciences Mice Endocrinology Immune system Insulin resistance Internal medicine Internal Medicine Medicine Animals Interferon gamma Receptor Glucagon-like peptide 1 receptor Cells Cultured Mice Inbred BALB C business.industry Liraglutide medicine.disease Fatty Liver Mice Inbred C57BL 030104 developmental biology Cytokine Female business medicine.drug |
| Zdroj: | Journal of diabetes and its complications. 31(9) |
| ISSN: | 1873-460X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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