| First Author | Lee JH | Year | 2013 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 304 |
| Issue | 10 | Pages | E1035-41 |
| PubMed ID | 23512810 | Mgi Jnum | J:198232 |
| Mgi Id | MGI:5495883 | Doi | 10.1152/ajpendo.00029.2013 |
| Citation | Lee JH, et al. (2013) Regulation of 11beta-HSD1 expression during adipose tissue expansion by hypoxia through different activities of NF-kappaB and HIF-1alpha. Am J Physiol Endocrinol Metab 304(10):E1035-41 |
| abstractText | 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is involved in the pathogenesis of type 2 diabetes by generating active glucocorticoids (cortisol and corticosterone) that are strong inhibitors of angiogenesis. However, the mechanism of 11beta-HSD1 gene expression and its relationship to adipose angiogenesis are largely unknown. To address this issue, we examined 11beta-HSD1 expression in visceral and subcutaneous adipose tissue (AT) of diet-induced obese (DIO) mice during weight gain and investigated the gene regulation by hypoxia in vitro. 11beta-HSD1 mRNA was reduced in the adipose tissues during weight gain in DIO mice, and the reduction was associated with an elevated expression of angiogenic factors. In vitro, 11beta-HSD1 expression was induced in mRNA and protein by hypoxia. Of the two transcription factors activated by hypoxia, the nuclear factor-kappaB (NF-kappaB) enhanced but the hypoxia inducible factor-1alpha (HIF-1alpha) reduced 11beta-HSD1 expression. 11beta-HSD1 expression was elevated by NF-kappaB in epididymal fat of aP2-p65 mice. The hypoxia-induced 11beta-HSD1 expression was attenuated by NF-kappaB inactivation in p65-deficient cells but enhanced by HIF-1 inactivation in HIF-1alpha-null cells. These data suggest that 11beta-HSD1 expression is upregulated by NF-kappaB and downregulated by HIF-1alpha. During AT expansion in DIO mice, the reduction of 11beta-HSD1 expression may reflect a dominant HIF-1alpha activity in the adipose tissue. This study suggests that NF-kappaB may mediate the inflammatory cytokine signal to upregulate 11beta-HSD1 expression. |
