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A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity
Open accessAbstract
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α 4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity. This adhesive interaction reciprocally and concomitantly modulated inflammatory activation of macrophages and downregulation of UCP1 expression dependent on the kinase Erk in adipocytes. Genetic or pharmacological inactivation of the integrin α 4 in mice resulted in elevated expression of UCP1 and beige adipogenesis of subcutaneous AT in obesity. Our findings, established in both mouse systems and human systems, reveal a self-sustained cycle of inflammation-driven impairment of beige adipogenesis in obesity.
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“A similar mechanism was found in human adipocytes as well [278].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [278]
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Metadata
- Authors
- Chung, K.-J., Chatzigeorgiou, A., Economopoulou, M., Garcia-Martin, R., Alexaki, V. I., Mitroulis, I., Nati, M., Gebler, J., Ziemssen, T., Goelz, S. E., Phieler, J., Lim, J.-H., Karalis, K. P., Papayannopoulou, T., Blüher, M., Hajishengallis, G., & Chavakis, T.
- Affiliations
- German Center for Diabetes Research (DE)
- Technische Universität Dresden (DE)
- Elan Pharmaceuticals, Inc. (Ireland) (IE)
- Biomedical Research Foundation of the Academy of Athens (GR)
- University of Washington (US)
- Leipzig University (DE)
- University of Pennsylvania (US)
- Corresponding author
- Chung, Kyoung-Jin
- Chavakis, Triantafyllos
- ORCID
- Venue
- Nature Immunology
- Published
- 2017-04-17
- Volume
- 18
- Issue
- 6
- Pages
- 654-664
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC5436941
- OpenAlex
- W2605432571
- Cited by
- 175
- References
- 68
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 18 · 2023: 13 · 2022: 14 · 2021: 19 · 2020: 26 · 2019: 23 · 2018: 30 · 2017: 8
- FWCI
- 17.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- National Institute of Dental and Craniofacial Research (R01DE024716, R37DE026152)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- obesity, beige adipogenesis, white adipose tissue inflammation, CD49d, VCAM-1, ERK kinase, UCP1, thermogenesis, adipose tissue macrophages
- MeSH terms
- Adipocytes, Beige, Uncoupling Protein 1, Adult, Aged, Aged, 80 and over, Animals, Cell Adhesion, Cell Differentiation, Feedback, Female, Humans, Inflammation, Macrophages, Male, Middle Aged, Monocytes, Obesity, RNA, Messenger, T-Lymphocytes, Immunoblotting, Down-Regulation, Adipocytes, Vascular Cell Adhesion Molecule-1, Integrin alpha4, 3T3-L1 Cells, Extracellular Signal-Regulated MAP Kinases, Subcutaneous Fat, Adipogenesis, Mice, Adipose Tissue, White, Gene Knockdown Techniques, Young Adult, Diet, High-Fat, Real-Time Polymerase Chain Reaction
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