Global and hepatocyte-specific ablation of Bmal1 induces hyperlipidaemia and enhances atherosclerosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10-10

AUTHORS

Xiaoyue Pan, Christopher A Bradfield, M Mahmood Hussain

ABSTRACT

Circadian rhythms controlled by clock genes affect plasma lipids. Here we show that global ablation of Bmal1 in Apoe-/- and Ldlr-/- mice and its liver-specific ablation in Apoe-/- (L-Bmal1-/-Apoe-/-) mice increases, whereas overexpression of BMAL1 in L-Bmal1-/-Apoe-/- and Apoe-/-mice decreases hyperlipidaemia and atherosclerosis. Bmal1 deficiency augments hepatic lipoprotein secretion and diminishes cholesterol excretion to the bile. Further, Bmal1 deficiency reduces expression of Shp and Gata4. Reductions in Shp increase Mtp expression and lipoprotein production, whereas reductions in Gata4 diminish Abcg5/Abcg8 expression and biliary cholesterol excretion. Forced SHP expression normalizes lipoprotein secretion with no effect on biliary cholesterol excretion, while forced GATA4 expression increases cholesterol excretion to the bile and reduces plasma lipids in L-Bmal1-/-Apoe-/- and Apoe-/- mice. Thus, our data indicate that Bmal1 modulates lipoprotein production and biliary cholesterol excretion by regulating the expression of Mtp and Abcg5/Abcg8 via Shp and Gata4. More... »

PAGES

13011

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms13011

DOI

http://dx.doi.org/10.1038/ncomms13011

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026947073

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27721414


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315 schema:name Departments of Cell Biology and Pediatrics, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
316 Winthrop University Hospital, Mineola, New York, USA.
317 rdf:type schema:Organization
318 https://www.grid.ac/institutes/grid.413926.b schema:alternateName VA NY Harbor Healthcare System
319 schema:name Departments of Cell Biology and Pediatrics, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
320 VA New York Harbor Healthcare System, Brooklyn, New York 11209, USA.
321 Winthrop University Hospital, Mineola, New York, USA.
322 rdf:type schema:Organization
 




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