Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice
Aims/hypothesis As obesity progresses, adipose tissue exhibits a hypoxic and inflammatory phenotype characterised by the infiltration of adipose tissue macrophages (ATMs). In this study, we examined how adipose tissue hypoxia is involved in the induction of the inflammatory M1 and anti-inflammatory...
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Published in: | Diabetologia Vol. 56; no. 6; pp. 1403 - 1412 |
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Main Authors: | , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Berlin/Heidelberg
Springer-Verlag
01-06-2013
Springer |
Subjects: | |
Online Access: | Get full text |
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Summary: | Aims/hypothesis
As obesity progresses, adipose tissue exhibits a hypoxic and inflammatory phenotype characterised by the infiltration of adipose tissue macrophages (ATMs). In this study, we examined how adipose tissue hypoxia is involved in the induction of the inflammatory M1 and anti-inflammatory M2 polarities of ATMs.
Methods
The hypoxic characteristics of ATMs were evaluated using flow cytometry after the injection of pimonidazole, a hypoxia probe, in normal-chow-fed or high-fat-fed mice. The expression of hypoxia-related and inflammation-related genes was then examined in M1/M2 ATMs and cultured macrophages.
Results
Pimonidazole uptake was greater in M1 ATMs than in M2 ATMs. This uptake was paralleled by the levels of inflammatory cytokines, such as TNF-α, IL-6 and IL-1β. The expression level of hypoxia-related genes, as well as inflammation-related genes, was also higher in M1 ATMs than in M2 ATMs. The expression of
Il6
,
Il1β
and
Nos2
in cultured macrophages was increased by exposure to hypoxia in vitro but was markedly decreased by the gene deletion of
Hif1a
. In contrast, the expression of
Tnf
, another inflammatory cytokine gene, was neither increased by exposure to hypoxia nor affected by
Hif1a
deficiency. These results suggest that hypoxia induces the inflammatory phenotypes of macrophages via
Hif1a
-dependent and -independent mechanisms. On the other hand, the expression of inflammatory genes in cultured M2 macrophages treated with IL-4 responded poorly to hypoxia.
Conclusions/interpretation
Adipose tissue hypoxia induces an inflammatory phenotype via
Hif1a
-dependent and
Hif1a
-independent mechanisms in M1 ATMs but not in M2 ATMs. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0012-186X 1432-0428 |
DOI: | 10.1007/s00125-013-2885-1 |