| First Author | Korach-André M | Year | 2011 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 301 |
| Issue | 1 | Pages | E210-22 |
| PubMed ID | 21521718 | Mgi Jnum | J:182063 |
| Mgi Id | MGI:5314675 | Doi | 10.1152/ajpendo.00541.2010 |
| Citation | Korach-Andre M, et al. (2011) Liver X receptors regulate de novo lipogenesis in a tissue-specific manner in C57BL/6 female mice. Am J Physiol Endocrinol Metab 301(1):E210-22 |
| abstractText | The liver X receptors (LXRs) play a key role in cholesterol and bile acid metabolism but are also important regulators of glucose metabolism. Recently, LXRs have been proposed as a glucose sensor affecting LXR-dependent gene expression. We challenged wild-type (WT) and LXRalphabeta(-/-) mice with a normal diet (ND) or a high-carbohydrate diet (HCD). Magnetic resonance imaging showed different fat distribution between WT and LXRalphabeta(-/-) mice. Surprisingly, gonadal (GL) adipocyte volume decreased on HCD compared with ND in WT mice, whereas it slightly increased in LXRalphabeta(-/-) mice. Interestingly, insulin-stimulated lipogenesis of isolated GL fat cells was reduced on HCD compared with ND in LXRalphabeta(-/-) mice, whereas no changes were observed in WT mice. Net de novo lipogenesis (DNL) calculated from Vo(2) and Vco(2) was significantly higher in LXRalphabeta(-/-) than in WT mice on HCD. Histology of HCD-fed livers showed hepatic steatosis in WT mice but not in LXRalphabeta(-/-) mice. Glucose tolerance was not different between groups, but insulin sensitivity was decreased by the HCD in WT but not in LXRalphabeta(-/-) mice. Finally, gene expression analysis of adipose tissue showed induced expression of genes involved in DNL in LXRalphabeta(-/-) mice compared with WT animals as opposed to the liver, where expression of DNL genes was repressed in LXRalphabeta(-/-) mice. We thus conclude that absence of LXRs stimulates DNL in adipose tissue, but suppresses DNL in the liver, demonstrating opposite roles of LXR in DNL regulation in these two tissues. These results show tissue-specific regulation of LXR activity, a crucial finding for drug development. |
