Cited by 175Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and Adiposity

A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity

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Chung, Kyoung-Jin, Chatzigeorgiou, Antonios, Economopoulou, Matina, Garcia-Martin, Ruben, Alexaki, Vasileia I, Mitroulis, Ioannis, Nati, Marina, Gebler, Janine +9 more·2017·Nature Immunology

Abstract

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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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
Venue
Nature Immunology
Published
2017-04-17
Volume
18
Issue
6
Pages
654-664
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
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
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 › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Epidemiology › 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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