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HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance.

Published on Dec 1, 2016in Diabetes7.20
· DOI :10.2337/db16-0012
Akiko Takikawa5
Estimated H-index: 5
(University of Toyama),
Arshad Mahmood15
Estimated H-index: 15
(University of Toyama)
+ 21 AuthorsKazuyuki Tobe66
Estimated H-index: 66
(University of Toyama)
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Abstract
Adipose tissue hypoxia is an important feature of pathological adipose tissue expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via VEGF-A. We previously reported that macrophages in crown-like structures (CLSs) are both hypoxic and inflammatory. In the present study, we examined how macrophage HIF-1α is involved in high-fat diet (HFD)-induced inflammation, neovascularization, hypoxia, and insulin resistance using mice with myeloid cell-specific HIF-1α deletion fed an HFD. Myeloid cell-specific HIF-1α gene deletion protected against HFD-induced inflammation, CLS formation, poor vasculature development in the adipose tissue, and systemic insulin resistance. Despite a reduced expression of Vegfa in eWAT, the preadipocytes and endothelial cells of HIF-1α-deficient mice expressed higher levels of angiogenic factors including Vegfa , Angpt1, Fgf1 , and Fgf10 in accordance with preferable eWAT remodeling. Our in vitro study revealed that LPS-treated bone marrow-derived macrophages directly inhibited the expression of angiogenic factors in 3T3-L1 preadipocytes. Thus, macrophage HIF-1α is involved in not only the formation of CLSs, further enhancing the inflammatory responses, but also the inhibition of neoangiogenesis in preadipocytes. We concluded that these two pathways contribute to the obesity-related physiology of pathological adipose tissue expansion, thus causing systemic insulin resistance.
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  • Citations (21)
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References44
Newest
#1Sung Sik Choe (SNU: Seoul National University)H-Index: 16
#2Kyung Cheul Shin (SNU: Seoul National University)H-Index: 4
Last.Jae Bum Kim (SNU: Seoul National University)H-Index: 39
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#1Yun Sok Lee (UCSD: University of California, San Diego)H-Index: 27
#2Jung Whan Kim (UCSD: University of California, San Diego)H-Index: 24
Last.Steven M. WatkinsH-Index: 35
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#1Yun Hee Lee (WSU: Wayne State University)H-Index: 7
#2Anelia P. Petkova (WSU: Wayne State University)H-Index: 8
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#1Hoon-Ki Sung (MSH: Mount Sinai Hospital, Toronto)H-Index: 19
#2Kyung Oh Doh (Yeungnam University)H-Index: 4
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#1Atsushi Obata (Kawasaki Medical School)H-Index: 7
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#1George Caputa (MPG: Max Planck Society)H-Index: 1
#2Angela Castoldi (MPG: Max Planck Society)H-Index: 1
Last.Edward J. Pearce (MPG: Max Planck Society)H-Index: 73
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#1Sander Lefere (UGent: Ghent University)H-Index: 4
#2F. Tacke (Charité)H-Index: 2
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