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Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity.

Alnaeeli M, Raaka BM, Gavrilova O, Teng R, Chanturiya T, Noguchi CT - Diabetes (2014)

Bottom Line: Using comprehensive in vivo and in vitro analyses in mice, EPO treatment inhibited WAT inflammation, normalized insulin sensitivity, and reduced glucose intolerance.Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like Mф and increased M2-like Mф in WAT, while decreasing inflammatory monocytes.These anti-inflammatory effects were found to be driven, at least in part, by direct EPO-R response in Mф via Stat3 activation, where EPO effects on M2 but not M1 Mф required interleukin-4 receptor/Stat6.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

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EPO treatment regulates Mф subtype composition in WAT. SVF cells from perigonadal fat were used for flow cytometry and analyses. Dot plots depict flow cytometry analysis of MGL-1+, MGL-1−, and CD11c+ Mф subsets (A), and their numbers per gram of WAT are shown (B). Expression levels of iNOS and IL-1β (C) and Arg-1, Fizz-1, and Ppar-γ (D) relative to β-actin were assessed. Results are shown as mean ± SEM for n = 5 mice per group, representative of three independent experiments with similar results. *P < 0.05; **P < 0.01.
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Figure 5: EPO treatment regulates Mф subtype composition in WAT. SVF cells from perigonadal fat were used for flow cytometry and analyses. Dot plots depict flow cytometry analysis of MGL-1+, MGL-1−, and CD11c+ Mф subsets (A), and their numbers per gram of WAT are shown (B). Expression levels of iNOS and IL-1β (C) and Arg-1, Fizz-1, and Ppar-γ (D) relative to β-actin were assessed. Results are shown as mean ± SEM for n = 5 mice per group, representative of three independent experiments with similar results. *P < 0.05; **P < 0.01.

Mentions: The effect of EPO administration on Mф population subtypes in WAT was examined. Using flow cytometry, EPO decreased MGL-1− and CD11c+ while increasing MGL-1+ Mф (Fig. 5A and B). qRT-PCR confirmed phenotypic Mф shift (Fig. 5C and D), showing that EPO reduced iNOS and Il-1β and increased Fizz-1, Ppar-γ, and Arg-1. Overall, EPO increased M2-like Mф and reduced M1-like Mф numbers, thus identifying and confirming its role in the regulation of not only Mф infiltration, but also local subtype polarization. Whether or not the conversion of M1- to M2-like Mф, as recently suggested (46), contributes to the observed EPO-mediated increase in MGL-1+ Mф remains unknown. Since M1/M2 nomenclature of Mф is based on in vitro studies, and may not represent in vivo Mф subtypes (17), we use the designation M1- and M2-like Mф to describe F4/80+MGL-1− and MGL-1+ cells, respectively.


Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity.

Alnaeeli M, Raaka BM, Gavrilova O, Teng R, Chanturiya T, Noguchi CT - Diabetes (2014)

EPO treatment regulates Mф subtype composition in WAT. SVF cells from perigonadal fat were used for flow cytometry and analyses. Dot plots depict flow cytometry analysis of MGL-1+, MGL-1−, and CD11c+ Mф subsets (A), and their numbers per gram of WAT are shown (B). Expression levels of iNOS and IL-1β (C) and Arg-1, Fizz-1, and Ppar-γ (D) relative to β-actin were assessed. Results are shown as mean ± SEM for n = 5 mice per group, representative of three independent experiments with similar results. *P < 0.05; **P < 0.01.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4066343&req=5

Figure 5: EPO treatment regulates Mф subtype composition in WAT. SVF cells from perigonadal fat were used for flow cytometry and analyses. Dot plots depict flow cytometry analysis of MGL-1+, MGL-1−, and CD11c+ Mф subsets (A), and their numbers per gram of WAT are shown (B). Expression levels of iNOS and IL-1β (C) and Arg-1, Fizz-1, and Ppar-γ (D) relative to β-actin were assessed. Results are shown as mean ± SEM for n = 5 mice per group, representative of three independent experiments with similar results. *P < 0.05; **P < 0.01.
Mentions: The effect of EPO administration on Mф population subtypes in WAT was examined. Using flow cytometry, EPO decreased MGL-1− and CD11c+ while increasing MGL-1+ Mф (Fig. 5A and B). qRT-PCR confirmed phenotypic Mф shift (Fig. 5C and D), showing that EPO reduced iNOS and Il-1β and increased Fizz-1, Ppar-γ, and Arg-1. Overall, EPO increased M2-like Mф and reduced M1-like Mф numbers, thus identifying and confirming its role in the regulation of not only Mф infiltration, but also local subtype polarization. Whether or not the conversion of M1- to M2-like Mф, as recently suggested (46), contributes to the observed EPO-mediated increase in MGL-1+ Mф remains unknown. Since M1/M2 nomenclature of Mф is based on in vitro studies, and may not represent in vivo Mф subtypes (17), we use the designation M1- and M2-like Mф to describe F4/80+MGL-1− and MGL-1+ cells, respectively.

Bottom Line: Using comprehensive in vivo and in vitro analyses in mice, EPO treatment inhibited WAT inflammation, normalized insulin sensitivity, and reduced glucose intolerance.Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like Mф and increased M2-like Mф in WAT, while decreasing inflammatory monocytes.These anti-inflammatory effects were found to be driven, at least in part, by direct EPO-R response in Mф via Stat3 activation, where EPO effects on M2 but not M1 Mф required interleukin-4 receptor/Stat6.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

Show MeSH
Related in: MedlinePlus