| First Author | Pan X | Year | 2010 |
| Journal | Cell Metab | Volume | 12 |
| Issue | 2 | Pages | 174-86 |
| PubMed ID | 20674862 | Mgi Jnum | J:163076 |
| Mgi Id | MGI:4821016 | Doi | 10.1016/j.cmet.2010.05.014 |
| Citation | Pan X, et al. (2010) Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP. Cell Metab 12(2):174-86 |
| abstractText | We examined the role of clock genes in the diurnal regulation of plasma triglyceride-rich apolipoprotein B-lipoproteins and their biosynthetic chaperone, microsomal triglyceride transfer protein (MTP). Clock(mt/mt) mice showed sustained hypertriglyceridemia and high MTP expression. CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box. SHP suppressed MTP expression by binding to the HNF4alpha/LRH-1 at the MTP promoter. Cyclic expression of MTP after serum shock was abrogated by siCLOCK and siSHP. Plasma triglyceride and MTP showed reduced diurnal variations in Shp(-/-) mice. Whereas peaks and nadirs in SHP expression were inversely correlated with those of MTP, these changes were reduced in Clock(mt/mt) mice. Expression of Shp abrogated hypertriglyceridemia in Clock(mt/mt) mice. Together, these studies describe a role of Clock/Shp in the diurnal regulation of MTP and plasma triglyceride and indicate that disruptions in circadian regulation might cause hyperlipidemia. |
