Fat-Produced Adipsin Regulates Inflammatory Arthritis
Summary: We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding “fat-free” (FF) mice completely lacking white and brown fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719306527 |
| _version_ | 1818195146041196544 |
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| author | Yongjia Li Wei Zou Jonathan R. Brestoff Nidhi Rohatgi Xiaobo Wu John P. Atkinson Charles A. Harris Steven L. Teitelbaum |
| author_facet | Yongjia Li Wei Zou Jonathan R. Brestoff Nidhi Rohatgi Xiaobo Wu John P. Atkinson Charles A. Harris Steven L. Teitelbaum |
| author_sort | Yongjia Li |
| collection | DOAJ |
| description | Summary: We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding “fat-free” (FF) mice completely lacking white and brown fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting a predisposition to severe IA. Surprisingly, FF mice are resistant to K/BxN serum-induced IA and attendant bone destruction. Despite robust systemic basal neutrophilia, neutrophil infiltration into joints of FF mice does not occur when challenged with K/BxN serum. Absence of adiponectin, leptin, or both has no effect on joint disease, but deletion of the adipokine adipsin (complement factor D) completely prevents serum-induced IA. Confirming that fat-expressed adipsin modulates the disorder, transplantation of wild-type (WT) adipose tissue into FF mice restores susceptibility to IA, whereas recipients of adipsin-deficient fat remain resistant. Thus, adipose tissue regulates development of IA through a pathway in which adipocytes modify neutrophil responses in distant tissues by producing adipsin. : The relationship of fat and inflammatory arthritis (IA) is poorly defined. Li et al. generate fat-free (FF) mice and observe that they are completely resistant to IA because of a lack of adipsin. Their studies provide evidence that fat regulates IA development by adipsin activation of the complement pathway. Keywords: inflammatory arthritis, adipsin, neutrophils |
| first_indexed | 2024-12-12T01:13:32Z |
| format | Article |
| id | doaj.art-5dd4250afadb4904aff14048960e40a9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T01:13:32Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5dd4250afadb4904aff14048960e40a92022-12-22T00:43:24ZengElsevierCell Reports2211-12472019-06-01271028092816.e3Fat-Produced Adipsin Regulates Inflammatory ArthritisYongjia Li0Wei Zou1Jonathan R. Brestoff2Nidhi Rohatgi3Xiaobo Wu4John P. Atkinson5Charles A. Harris6Steven L. Teitelbaum7Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Corresponding authorSummary: We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding “fat-free” (FF) mice completely lacking white and brown fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting a predisposition to severe IA. Surprisingly, FF mice are resistant to K/BxN serum-induced IA and attendant bone destruction. Despite robust systemic basal neutrophilia, neutrophil infiltration into joints of FF mice does not occur when challenged with K/BxN serum. Absence of adiponectin, leptin, or both has no effect on joint disease, but deletion of the adipokine adipsin (complement factor D) completely prevents serum-induced IA. Confirming that fat-expressed adipsin modulates the disorder, transplantation of wild-type (WT) adipose tissue into FF mice restores susceptibility to IA, whereas recipients of adipsin-deficient fat remain resistant. Thus, adipose tissue regulates development of IA through a pathway in which adipocytes modify neutrophil responses in distant tissues by producing adipsin. : The relationship of fat and inflammatory arthritis (IA) is poorly defined. Li et al. generate fat-free (FF) mice and observe that they are completely resistant to IA because of a lack of adipsin. Their studies provide evidence that fat regulates IA development by adipsin activation of the complement pathway. Keywords: inflammatory arthritis, adipsin, neutrophilshttp://www.sciencedirect.com/science/article/pii/S2211124719306527 |
| spellingShingle | Yongjia Li Wei Zou Jonathan R. Brestoff Nidhi Rohatgi Xiaobo Wu John P. Atkinson Charles A. Harris Steven L. Teitelbaum Fat-Produced Adipsin Regulates Inflammatory Arthritis Cell Reports |
| title | Fat-Produced Adipsin Regulates Inflammatory Arthritis |
| title_full | Fat-Produced Adipsin Regulates Inflammatory Arthritis |
| title_fullStr | Fat-Produced Adipsin Regulates Inflammatory Arthritis |
| title_full_unstemmed | Fat-Produced Adipsin Regulates Inflammatory Arthritis |
| title_short | Fat-Produced Adipsin Regulates Inflammatory Arthritis |
| title_sort | fat produced adipsin regulates inflammatory arthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719306527 |
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