| First Author | Esteves CL | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 5 | Pages | e37953 |
| PubMed ID | 22662254 | Mgi Jnum | J:187301 |
| Mgi Id | MGI:5436173 | Doi | 10.1371/journal.pone.0037953 |
| Citation | Esteves CL, et al. (2012) Regulation of adipocyte 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by CCAAT/enhancer-binding protein (C/EBP) beta isoforms, LIP and LAP. PLoS One 7(5):e37953 |
| abstractText | 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses intracellular regeneration of active glucocorticoids, notably in liver and adipose tissue. 11beta-HSD1 is increased selectively in adipose tissue in human obesity, a change implicated in the pathogenesis of metabolic syndrome. With high fat (HF)-feeding, adipose tissue 11beta-HSD1 is down-regulated in mice, plausibly to counteract metabolic disease. Transcription of 11beta-HSD1 is directly regulated by members of the CCAAT/enhancer binding protein (C/EBP) family. Here we show that while total C/EBPbeta in adipose tissue is unaltered by HF diet, the ratio of the C/EBPbeta isoforms liver-enriched inhibitor protein (LIP) and liver-enriched activator protein (LAP) (C/EBPbeta-LIP:LAP) is increased in subcutaneous adipose. This may cause changes in 11beta-HSD1 expression since genetically modified C/EBPbeta((+/L)) mice, with increased C/EBPbeta-LIP:LAP ratio, have decreased subcutaneous adipose 11beta-HSD1 mRNA levels, whereas C/EBPbeta(DeltauORF) mice, with decreased C/EBPbeta-LIP:LAP ratio, show increased subcutaneous adipose 11beta-HSD1. C/EBPbeta-LIP:LAP ratio is regulated by endoplasmic reticulum (ER) stress and mTOR signalling, both of which are altered in obesity. In 3T3-L1 adipocytes, 11beta-HSD1 mRNA levels were down-regulated following induction of ER stress by tunicamycin but were up-regulated following inhibition of mTOR by rapamycin. These data point to a central role for C/EBPbeta and its processing to LIP and LAP in transcriptional regulation of 11beta-HSD1 in adipose tissue. Down-regulation of 11beta-HSD1 by increased C/EBPbeta-LIP:LAP in adipocytes may be part of a nutrient-sensing mechanism counteracting nutritional stress generated by HF diet. |
