| LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of Wnt signaling. | |
| | |
MedLine Citation:
|
PMID: 18990694 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1-deficient fibroblasts accumulate high levels of intracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently of the noradrenergic pathway, through inhibition of GSK3beta and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals. |
| | |
Authors:
|
Jérome Terrand; Véronique Bruban; Li Zhou; Wanfeng Gong; Zeina El Asmar; Petra May; Kai Zurhove; Philipp Haffner; Claude Philippe; Estelle Woldt; Rachel L Matz; Céline Gracia; Daniel Metzger; Johan Auwerx; Joachim Herz; Philippe Boucher |
Related Documents
:
|
15666804 - Multiple contributions from long-chain fatty acid metabolism in y-1 and ma-10 cells. 2051884 - Effect of trans fatty acids on plasma lipids, platelet function and systolic blood pres... 16751234 - Singlet oxygen generation by uva light exposure of endogenous photosensitizers. 913354 - Adrenal testis inter-relationship in male indian palm squirrel funambulus pennanti wrou... 18656924 - Changes in phenolic concentrations during recurrent selection for resistance to the med... 10696114 - Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is dev... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-11-06 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 284 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Jan |
Date Detail:
|
Created Date: 2008-12-29 Completed Date: 2009-02-24 Revised Date: 2011-11-02 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 381-8 Citation Subset: IM |
Affiliation:
|
CNRS, UMR7175, Université de Strasbourg, Illkirch, F-67401 France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetyl-CoA Carboxylase
/
genetics,
metabolism Adipocytes / cytology, metabolism* Animals Cell Differentiation / physiology Cells, Cultured Cholesterol / genetics, metabolism Fatty Acids / biosynthesis, genetics Glycogen Synthase Kinase 3 / genetics, metabolism Humans Lipid Metabolism / physiology* Liver / cytology, metabolism Mice Mice, Knockout Proto-Oncogene Proteins / genetics, metabolism* Receptors, LDL / genetics, metabolism* Signal Transduction / physiology* Tumor Suppressor Proteins / genetics, metabolism* Wnt Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
DK067320/DK/NIDDK NIH HHS; HL20948/HL/NHLBI NIH HHS; HL63762/HL/NHLBI NIH HHS; NS43408/NS/NINDS NIH HHS; R37 HL063762-12/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids; 0/Lrp1 protein, mouse; 0/Proto-Oncogene Proteins; 0/Receptors, LDL; 0/Tumor Suppressor Proteins; 0/WNT5A protein, human; 0/Wnt Proteins; 0/Wnt5a protein, mouse; 57-88-5/Cholesterol; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 6.4.1.2/Acetyl-CoA Carboxylase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Characterization of the complement inhibitory function of rhesus rhadinovirus complement control pro...
Next Document: Met receptor tyrosine kinase degradation is altered in response to the leucine-rich repeat of the Li...