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Cited by 415Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

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Hill, David A., Lim, Hee-Woong, Kim, Yong Hoon, Ho, Wesley Y., Foong, Yee Hoon, Nelson, Victoria L., Nguyen, Hoang C. B., Chegireddy, Kavya +6 more·2018·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1802611115PMC PMC5984532
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Abstract

Significance: Obesity has reached pandemic levels, prompting the need for novel therapeutics. The immune system has been suggested to be critically linked to metabolic health, leading to the prospect of immune-directed therapies. We report that obese fat tissue contains multiple distinct populations of macrophages with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. These results provide a higher resolution of the cellular and functional heterogeneity within adipose macrophages and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related inflammatory comorbidities.

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  • This epigenetic signature is also seen in macrophages in atherosclerosis models and adipose-associated macrophages, but this signature is not seen in DAM microglia.

    “This epigenetic signature is also seen in macrophages in atherosclerosis models23 and adipose-associated macrophages24 but this signature is not seen in DAM microglia25.”

    From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [24]

  • 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 Hill et al., 2018

    The Abstract and Discussion discuss macrophage populations in adipose tissue, not microglia in the hypothalamus. Searches for hypothalamic microglia and obesity onset or progression found no passage in our copy addressing that claim; the paper’s adipose-tissue findings do not establish it. (LLM, conf=0.76)

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Authors
Hill, D. A., Lim, H.-W., Kim, Y. H., Ho, W. Y., Foong, Y. H., Nelson, V. L., Nguyen, H. C. B., Chegireddy, K., Kim, J., Habertheuer, A., Vallabhajosyula, P., Kambayashi, T., Won, K.-J., & Lazar, M. A.
Affiliations
  • Children's Hospital of Philadelphia (US)
  • University of Pennsylvania (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2018-05-14
Volume
115
Issue
22
Pages
E5096-E5105
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1802611115
PMC
PMC5984532
OpenAlex
W2804734969
Cited by
415
References
11
Citations by year
2026: 30 · 2025: 54 · 2024: 56 · 2023: 60 · 2022: 62 · 2021: 72 · 2020: 50 · 2019: 23 · 2018: 6
FWCI
29.48
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 184 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK49780)
  • HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32 HD043021)
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, obesity, crown-like structures, macrophage heterogeneity, adipose tissue inflammation, lipid-laden macrophages, adoptive transfer, chromatin landscape, transcriptome
MeSH terms
Adipose Tissue, Animals, Female, Humans, Inflammation, Macrophages, Mice, Inbred C57BL, Obesity, Mice, Exosomes, Transcriptome, Tetraspanin 29

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