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Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation.

PLoS ONE. 2014;9(4):e93856 DOI 10.1371/journal.pone.0093856


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Journal Title: PLoS ONE

ISSN: 1932-6203 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Medicine | Science

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML



Yoshitaka Kihira

Mariko Miyake

Manami Hirata

Yoji Hoshina

Kana Kato

Hitoshi Shirakawa

Hiroshi Sakaue

Noriko Yamano

Yuki Izawa-Ishizawa

Keisuke Ishizawa

Yasumasa Ikeda

Koichiro Tsuchiya

Toshiaki Tamaki

Shuhei Tomita


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Time From Submission to Publication: 24 weeks


Abstract | Full Text

It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue.