Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation.
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...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093856&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yoshitaka Kihira |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a5d0ff6c263f4ca682d049eede2aae2c |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-a5d0ff6c263f4ca682d049eede2aae2c2025-08-20T02:15:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9385610.1371/journal.pone.0093856Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation.Yoshitaka KihiraMariko MiyakeManami HirataYoji HoshinaKana KatoHitoshi ShirakawaHiroshi SakaueNoriko YamanoYuki Izawa-IshizawaKeisuke IshizawaYasumasa IkedaKoichiro TsuchiyaToshiaki TamakiShuhei TomitaIt 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093856&type=printable |
| spellingShingle | 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 Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. PLoS ONE |
| title | Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. |
| title_full | Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. |
| title_fullStr | Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. |
| title_full_unstemmed | Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. |
| title_short | Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. |
| title_sort | deletion of hypoxia inducible factor 1α in adipocytes enhances glucagon like peptide 1 secretion and reduces adipose tissue inflammation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093856&type=printable |
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