| First Author | Su W | Year | 2017 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 312 |
| Issue | 4 | Pages | E357-E367 |
| PubMed ID | 28270440 | Mgi Jnum | J:244941 |
| Mgi Id | MGI:5913720 | Doi | 10.1152/ajpendo.00310.2016 |
| Citation | Su W, et al. (2017) Liver X receptor alpha induces 17beta-hydroxysteroid dehydrogenase-13 expression through SREBP-1c. Am J Physiol Endocrinol Metab 312(4):E357-E367 |
| abstractText | Liver X receptors, including LXRalpha and LXRbeta, are known to be master regulators of liver lipid metabolism. Activation of LXRalpha increases hepatic lipid storage in lipid droplets (LDs). 17beta-Hydroxysteroid dehydrogenase-13 (17beta-HSD13), a recently identified liver-specific LD-associated protein, has been reported to be involved in the development of nonalcoholic fatty liver disease. However, little is known about its transcriptional regulation. In the present study, we aimed at determining whether 17beta-HSD13 gene transcription is controlled by LXRs. We found that treatment with T0901317, a nonspecific LXR agonist, increased both 17beta-HSD13 mRNA and protein levels in cultured hepatocytes. It also significantly upregulated hepatic 17beta-HSD13 expression in wild-type (WT) and LXRbeta-/- mice but not in LXRalpha-/- mice. Basal expression of 17beta-HSD13 in the livers of LXRalpha-/- mice was lower than that in the livers of WT and LXRbeta-/- mice. Moreover, induction of hepatic 17beta-HSD13 expression by T0901317 was almost completely abolished in SREBP-1c-/- mice. Bioinformatics analysis revealed a consensus sterol regulatory element (SRE)-binding site in the promoter region of the 17beta-HSD13 gene. A 17beta-HSD13 gene promoter-driven luciferase reporter and ChIP assays further confirmed that the 17beta-HSD13 gene was under direct control of SREBP-1c. Collectively, these findings demonstrate that LXRalpha activation induces 17beta-HSD13 expression in a SREBP-1c-dependent manner. 17beta-HSD13 may be involved in the development of LXRalpha-mediated fatty liver. |
