Metabolically activated adipose tissue macrophages perform detrimental and beneficial functions during diet-induced obesity.
Open accessAbstract
During obesity, adipose tissue macrophages (ATMs) adopt a metabolically activated (MMe) phenotype. However, the functions of MMe macrophages are poorly understood. Here, we combine proteomic and functional methods to demonstrate that, in addition to potentiating inflammation, MMe macrophages promote dead adipocyte clearance through lysosomal exocytosis. We identify NADPH oxidase 2 (NOX2) as a driver of the inflammatory and adipocyte-clearing properties of MMe macrophages and show that, compared to wild-type, Nox2 −/− mice exhibit a time-dependent metabolic phenotype during diet-induced obesity. After 8 weeks of high-fat feeding, Nox2 −/− mice exhibit attenuated ATM inflammation and mildly improved glucose tolerance. After 16 weeks of high-fat feeding, Nox2 −/− mice develop severe insulin resistance, hepatosteatosis, and visceral lipoatrophy characterized by dead adipocyte accumulation and defective ATM lysosomal exocytosis, a phenotype reproduced in myeloid cell-specific Nox2 −/− mice. Collectively, our findings suggest that MMe macrophages perform detrimental and beneficial functions whose contribution to metabolic phenotypes during obesity is determined by disease progression.
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Microglia within the hypothalamus affect the progression and onset of obesity.
“recent studies have demonstrated that microglia, in particular microglia within the hypothalamus, affects the progression and onset of obesity (Coats et al., 2017; Valdearcos et al., 2017, 2019; Hill et al., 2018).”
From Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice (2022) · cites this paper as Coats et al., 2017
The Introduction and Results discuss macrophages in adipose tissue during diet-induced obesity, not microglia in the hypothalamus. Searches for hypothalamic microglia and their role in obesity onset or progression found no passage in our copy addressing that claim; the Discussion’s mention of brain injury does not establish it. (LLM, conf=0.74)
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“This is relevant in the context of metabolism because recent studies have demonstrated that microglia, in particular microglia within the hypothalamus, affects the progression and onset of obesity (Coats et al., 2017; Valdearcos et al., 2017, 2019; Hill et al., 2018).”
Background
- Authors
- Coats, B. R., Schoenfelt, K. Q., Barbosa-Lorenzi, V. C., Peris, E., Cui, C., Hoffman, A., Zhou, G., Fernandez, S., Zhai, L., Hall, B. A., Haka, A. S., Shah, A. M., Reardon, C. A., Brady, M. J., Rhodes, C. J., Maxfield, F. R., & Becker, L.
- Affiliations
- University of Chicago (US)
- Weill Cornell Medicine (US)
- King's College London (GB)
- Corresponding author
- Becker, Lev
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 20
- Issue
- 13
- Pages
- 3149-3161
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5646237
- OpenAlex
- W2759584129
- Cited by
- 291
- References
- 10
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 40 · 2023: 29 · 2022: 36 · 2021: 41 · 2020: 36 · 2019: 42 · 2018: 15
- FWCI
- 19.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (R01DK102960, R37DK27083, R01HL093324, R01DK055267, P30 DK020595, T32DK087703, T32DK007074)
- Bernice Goldblatt Endowment Fellowship
- University of Chicago
- American Heart Association (10SDG3600027)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- adipose tissue macrophages, diet-induced obesity, NADPH oxidase 2, NOX2, lysosomal exocytosis, adipose tissue inflammation, insulin resistance, hepatic steatosis, glucose tolerance, high-fat diet
- MeSH terms
- Adipose Tissue, Animals, Humans, Macrophages, Obesity, Mice, Diet, High-Fat
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