| Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP. | |
| | |
MedLine Citation:
|
PMID: 20674862 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Xiaoyue Pan; Yuxia Zhang; Li Wang; M Mahmood Hussain |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Cell metabolism Volume: 12 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-02 Completed Date: 2010-11-22 Revised Date: 2012-05-09 |
Medline Journal Info:
|
Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
|
Languages: eng Pagination: 174-86 Citation Subset: IM |
Copyright Information:
|
Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Cell Biology and Pediatrics, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals CLOCK Proteins / genetics, metabolism* Carrier Proteins / metabolism* Cell Line, Tumor Circadian Rhythm / physiology* Humans Liver / metabolism Male Mice Mice, Inbred C57BL Promoter Regions, Genetic Protein Binding RNA Interference RNA, Small Interfering / metabolism Receptors, Cytoplasmic and Nuclear / deficiency, genetics, metabolism* Triglycerides / blood* |
| Grant Support | |
ID/Acronym/Agency:
|
DK-080440/DK/NIDDK NIH HHS; DK-81879/DK/NIDDK NIH HHS; R01 DK046900-14/DK/NIDDK NIH HHS; R01 DK046900-16/DK/NIDDK NIH HHS; R01 DK080440-04/DK/NIDDK NIH HHS; R01 DK081879/DK/NIDDK NIH HHS; R01 DK081879-01A1/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Carrier Proteins; 0/RNA, Small Interfering; 0/Receptors, Cytoplasmic and Nuclear; 0/Triglycerides; 0/microsomal triglyceride transfer protein; 0/nuclear receptor subfamily 0, group B, member 2; EC 2.3.1.48/CLOCK Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Identification of surface residues on Niemann-Pick C2 essential for hydrophobic handoff of cholester...
Next Document: Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from athero...