| First Author | Kihira Y | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 4 | Pages | e93856 |
| PubMed ID | 24705496 | Mgi Jnum | J:215021 |
| Mgi Id | MGI:5604551 | Doi | 10.1371/journal.pone.0093856 |
| Citation | Kihira Y, et al. (2014) Deletion of hypoxia-inducible factor-1alpha in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation. PLoS One 9(4):e93856 |
| abstractText | It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1alpha. Although some studies have shown that the expression of HIF-1alpha 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-1alpha 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 alpha (TNFalpha) 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-1alpha in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue. |
