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Cited by 370

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Dynamic, M2-Like Remodeling Phenotypes of CD11c+ Adipose Tissue Macrophages During High-Fat Diet–Induced Obesity in Mice

Open access
Shaul, Merav E., Bennett, Grace, Strissel, Katherine J., Greenberg, Andrew S., Obin, Martin S.·2010·Diabetes
DOI 10.2337/db09-1402
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Abstract

OBJECTIVE: To identify, localize, and determine M1/M2 polarization of epidydimal adipose tissue (eAT) macrophages (Φs) during high-fat diet (HFD)-induced obesity. RESEARCH DESIGN AND METHODS: Male C57BL/6 mice were fed an HFD (60% fat kcal) or low-fat diet (LFD) (10% fat kcal) for 8 or 12 weeks. eATMΦs (F4/80+ cells) were characterized by in vivo fluorescent labeling, immunohistochemistry, fluorescence-activated cell sorting, and quantitative PCR. RESULTS: Recruited interstitial macrophage galactose-type C-type lectin (MGL)1+/CD11c− and crown-like structure–associated MGL1−/CD11c+ and MGL1med/CD11c+ eATMΦs were identified after 8 weeks of HFD. MGL1med/CD11c+ cells comprised ∼65% of CD11c+ eATMΦs. CD11c+ eATMΦs expressed a mixed M1/M2 profile, with some M1 transcripts upregulated (IL-12p40 and IL-1β), others downregulated (iNOS, caspase-1, MCP-1, and CD86), and multiple M2 and matrix remodeling transcripts upregulated (arginase-1, IL-1Ra, MMP-12, ADAM8, VEGF, and Clec-7a). At HFD week 12, each eATMΦ subtype displayed an enhanced M2 phenotype as compared with HFD week 8. CD11c+ subtypes downregulated IL-1β and genes mediating antigen presentation (I-a, CD80) and upregulated the M2 hallmark Ym-1 and genes promoting oxidative metabolism (PGC-1α) and adipogenesis (MMP-2). MGL1med/CD11c+ eATMΦs upregulated additional M2 genes (IL-13, SPHK1, CD163, LYVE-1, and PPAR-α). MGL1med/CD11c+ ATMΦs expressing elevated PGC-1α, PPAR-α, and Ym-1 transcripts were selectively enriched in eAT of obese mice fed pioglitazone for 6 days, confirming the M2 features of the MGL1med/CD11c+ eATMΦ transcriptional profile and implicating PPAR activation in its elicitation. CONCLUSIONS: These results 1) redefine the phenotypic potential of CD11c+ eATMΦs and 2) suggest previously unappreciated phenotypic and functional commonality between murine and human ATMΦs in the development of obesity and its complications.

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Metadata

Authors
Shaul, M. E., Bennett, G., Strissel, K. J., Greenberg, A. S., & Obin, M. S.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2010-02-25
Volume
59
Issue
5
Pages
1171-1181
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db09-1402
OpenAlex
W2149332882
Cited by
370
References
10
FWCI
23.48
Type
journal article
Language
en
Open access
hybrid

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