Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ

Low-density lipoprotein receptor-related protein 1 (LRP1) regulates lipid and glucose metabolism in liver and adipose tissue. It is also involved in central nervous system regulation of food intake and leptin signalling. Here we demonstrate that endothelial Lrp1 regulates systemic energy homeostasis...

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Autores principales: Mao, Hua, Lockyer, Pamela, Li, Luge, Ballantyne, Christie M., Patterson, Cam, Xie, Liang, Pi, Xinchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394236/
https://www.ncbi.nlm.nih.gov/pubmed/28393867
http://dx.doi.org/10.1038/ncomms14960
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author Mao, Hua
Lockyer, Pamela
Li, Luge
Ballantyne, Christie M.
Patterson, Cam
Xie, Liang
Pi, Xinchun
author_facet Mao, Hua
Lockyer, Pamela
Li, Luge
Ballantyne, Christie M.
Patterson, Cam
Xie, Liang
Pi, Xinchun
author_sort Mao, Hua
collection PubMed
description Low-density lipoprotein receptor-related protein 1 (LRP1) regulates lipid and glucose metabolism in liver and adipose tissue. It is also involved in central nervous system regulation of food intake and leptin signalling. Here we demonstrate that endothelial Lrp1 regulates systemic energy homeostasis. Mice with endothelial-specific Lrp1 deletion display improved glucose sensitivity and lipid profiles combined with increased oxygen consumption during high-fat-diet-induced obesity. We show that the intracellular domain of Lrp1 interacts with the nuclear receptor Pparγ, a central regulator of lipid and glucose metabolism, acting as its transcriptional co-activator in endothelial cells. Therefore, Lrp1 not only acts as an endocytic receptor but also directly participates in gene transcription. Our findings indicate an underappreciated functional role of endothelium in maintaining systemic energy homeostasis.
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spelling pubmed-53942362017-05-17 Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ Mao, Hua Lockyer, Pamela Li, Luge Ballantyne, Christie M. Patterson, Cam Xie, Liang Pi, Xinchun Nat Commun Article Low-density lipoprotein receptor-related protein 1 (LRP1) regulates lipid and glucose metabolism in liver and adipose tissue. It is also involved in central nervous system regulation of food intake and leptin signalling. Here we demonstrate that endothelial Lrp1 regulates systemic energy homeostasis. Mice with endothelial-specific Lrp1 deletion display improved glucose sensitivity and lipid profiles combined with increased oxygen consumption during high-fat-diet-induced obesity. We show that the intracellular domain of Lrp1 interacts with the nuclear receptor Pparγ, a central regulator of lipid and glucose metabolism, acting as its transcriptional co-activator in endothelial cells. Therefore, Lrp1 not only acts as an endocytic receptor but also directly participates in gene transcription. Our findings indicate an underappreciated functional role of endothelium in maintaining systemic energy homeostasis. Nature Publishing Group 2017-04-10 /pmc/articles/PMC5394236/ /pubmed/28393867 http://dx.doi.org/10.1038/ncomms14960 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Mao, Hua
Lockyer, Pamela
Li, Luge
Ballantyne, Christie M.
Patterson, Cam
Xie, Liang
Pi, Xinchun
Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
title Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
title_full Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
title_fullStr Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
title_full_unstemmed Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
title_short Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
title_sort endothelial lrp1 regulates metabolic responses by acting as a co-activator of pparγ
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394236/
https://www.ncbi.nlm.nih.gov/pubmed/28393867
http://dx.doi.org/10.1038/ncomms14960
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