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Cited by 699Peroxisome Proliferator-Activated ReceptorsAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Adipocyte-Derived Th2 Cytokines and Myeloid PPARδ Regulate Macrophage Polarization and Insulin Sensitivity

Open access
Kang, Kihwa, Reilly, Shannon M., Karabacak, Volkan, Gangl, Matthew R., Fitzgerald, Kelly, Hatano, Ben, Lee, Chih-Hao·2008·Cell Metabolism
DOI 10.1016/j.cmet.2008.04.002PMC PMC2586840
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Abstract

The polarization of adipose tissue-resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to improve insulin sensitivity. However, the mechanisms controlling tissue macrophage activation remain unclear. Here we show that adipocytes are a source of Th2 cytokines, including IL-13 and to a lesser extent IL-4, which induce macrophage PPARdelta/beta (Ppard/b) expression through a STAT6 binding site on its promoter to activate alternative activation. Coculture studies indicate that Ppard ablation renders macrophages incapable of transition to the M2 phenotype, which in turns causes inflammation and metabolic derangement in adipocytes. Remarkably, a similar regulatory mechanism by hepatocyte-derived Th2 cytokines and macrophage PPARdelta is found to control hepatic lipid metabolism. The physiological relevance of this paracrine pathway is demonstrated in myeloid-specific PPARdelta(-/-) mice, which develop insulin resistance and show increased adipocyte lipolysis and severe hepatosteatosis. These findings provide a molecular basis to modulate tissue-resident macrophage activation and insulin sensitivity.

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Crossref · 10.1016/j.cmet.2008.04.002

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Metadata

Authors
Kang, K., Reilly, S. M., Karabacak, V., Gangl, M. R., Fitzgerald, K., Hatano, B., & Lee, C.-H.
Affiliations
Harvard University (US)
Corresponding author
Lee, Chih-Hao
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2008-06
Volume
7
Issue
6
Pages
485-495
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2008.04.002
PMC
PMC2586840
OpenAlex
W2046935888
Cited by
699
References
41
Citations by year
2026: 14 · 2025: 24 · 2024: 25 · 2023: 21 · 2022: 25 · 2021: 44 · 2020: 42 · 2019: 32 · 2018: 39 · 2017: 40 · 2016: 43 · 2015: 46 · 2014: 40 · 2013: 76 · 2012: 51
FWCI
18.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5t32es007155-24)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK34845, R90DK071507, R01DK075046, P30DK034854)
  • National Institute of Environmental Health Sciences (T32-ES07155, T32-ES007155, T32ES016645)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords
adipose tissue macrophages, macrophage polarization, M2 phenotype, Th2 cytokines, IL-13, IL-4, PPARδ, STAT6, adipocytes, hepatocytes, insulin sensitivity, insulin resistance, hepatic lipid metabolism, hepatic steatosis, adipocyte lipolysis, paracrine signaling, myeloid-specific knockout
MeSH terms
Animals, Gene Expression Regulation, Inflammation, Insulin Resistance, Macrophage Activation, Macrophages, Promoter Regions, Genetic, Cytokines, Adipocytes, Mice, Knockout, Th2 Cells, Coculture Techniques, Paracrine Communication, Hepatocytes, PPAR delta, PPAR-beta, Lipid Metabolism, Mice

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