Inhibition of p38mapk reduces adipose tissue inflammation in aging mediated by arginase-II
- Huang, Ji Cardiovascular and Aging Research, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland - National Center of Competence in Research “Kidney.CH”, Zurich, Switzerland
- Liu, Chang Cardiovascular and Aging Research, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
- Ming, Xiu-Fen Cardiovascular and Aging Research, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland - National Center of Competence in Research “Kidney.CH”, Zurich, Switzerland
- Yang, Zhihong Cardiovascular and Aging Research, Department of Endocrinology, Metabolism, and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland - National Center of Competence in Research “Kidney.CH”, Zurich, Switzerland
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2020
Published in:
- Pharmacology. - 2020, vol. 105, no. 9–10, p. 491–504
English
Background: Adipose tissue inflammation occurs not only in obesity but also in aging and is mechanistically linked with age-associated diseases. Studies show that ablation of the l-arginine-metabolizing enzyme arginase-II (Arg-II) reduces adipose tissue inflammation and improves glucose tolerance in obesity. However, the role of Arg-II in aging adipose tissue inflammation is not clear. Objective: This study investigated the role of Arg-II in age-associated adipose tissue inflammation. Methods: Visceral adipose tissues of young (3–6 months) and old (20–24 months) wild-type (WT) and Arg-II−/− mice were investigated. Immunofluorescence confocal microscopy was performed for analysis of macrophage accumulation and cellular localization of arginase and cytokines; expression of arginase and cytokines was analyzed by qRT-PCR or immunoblotting or ELISA; activation of mitogen-activated protein kinases in adipose tissues was analyzed by immunoblotting; and arginase activity was measured by colorimetric determination of urea production. Results: In the old WT mice, there is more macrophage accumulation in the visceral adipose tissues than in Arg-II knockout animals. An age-associated increase in arginase activity and Arg-II expression in adipose tissues of WT mice is observed. Arg-II knockout enhances Arg-I expression and activity, but inhibits interleukin (IL)-6 expression and secretion and reduces active p38mapk in aging adipose tissue macrophages and stromal cells. Treatment of aging adipose tissues of WT mice with a specific p38mapk inhibitor SB203580 reduces IL-6 secretion. Conclusions: Arg-II promotes IL-6 production in aging adipose tissues through p38mapk. The results suggest that targeting Arg-II or inhibiting p38mapk could be beneficial in reducing age-associated adipose tissue inflammation.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 329909
- DOI 10.1159/000507635
- Persistent URL
- https://folia.unifr.ch/unifr/documents/309189
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