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Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis

Brown adipose tissue dissipates energy in the form of heat. Recent studies have shown that adult humans possess both classical brown and beige adipocytes (brown-like adipocytes in white adipose tissue, WAT), and stimulating brown and beige adipocyte formation can be a new avenue to treat obesity. An...

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Autores principales: Than, Aung, Xu, Shaohai, Li, Ru, Leow, Melvin Khee-Shing, Sun, Lei, Chen, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661636/
https://www.ncbi.nlm.nih.gov/pubmed/29263921
http://dx.doi.org/10.1038/sigtrans.2017.22
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author Than, Aung
Xu, Shaohai
Li, Ru
Leow, Melvin Khee-Shing
Sun, Lei
Chen, Peng
author_facet Than, Aung
Xu, Shaohai
Li, Ru
Leow, Melvin Khee-Shing
Sun, Lei
Chen, Peng
author_sort Than, Aung
collection PubMed
description Brown adipose tissue dissipates energy in the form of heat. Recent studies have shown that adult humans possess both classical brown and beige adipocytes (brown-like adipocytes in white adipose tissue, WAT), and stimulating brown and beige adipocyte formation can be a new avenue to treat obesity. Angiotensin II (AngII) is a peptide hormone that plays important roles in energy metabolism via its angiotensin type 1 or type 2 receptors (AT1R and AT2R). Adipose tissue is a major source of AngII and expresses both types of its receptors, implying the autocrine and paracrine role of AngII in regulating adipose functions and self-remodeling. Here, based on the in vitro studies on primary cultures of mouse white adipocytes, we report that, AT2R activation, either by AngII or AT2R agonist (C21), induces white adipocyte browning, by increasing PPARγ expression, at least in part, via ERK1/2, PI3kinase/Akt and AMPK signaling pathways. It is also found that AngII–AT2R enhances brown adipogenesis. In the in vivo studies on mice, administration of AT1R antagonist (ZD7155) or AT2R agonist (C21) leads to the increase of WAT browning, body temperature and serum adiponectin, as well as the decrease of WAT mass and the serum levels of TNFα, triglycerides and free fatty acids. In addition, AT2R-induced browning effect is also observed in human white adipocytes, as evidenced by the increased UCP1 expression and oxygen consumption. Finally, we provide evidence that AT2R plays important roles in hormone T3-induced white adipose browning. This study, for the first time, reveals the browning and brown adipogenic effects of AT2R and suggests a potential therapeutic target to combat obesity and related metabolic disorders.
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spelling pubmed-56616362017-12-20 Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis Than, Aung Xu, Shaohai Li, Ru Leow, Melvin Khee-Shing Sun, Lei Chen, Peng Signal Transduct Target Ther Article Brown adipose tissue dissipates energy in the form of heat. Recent studies have shown that adult humans possess both classical brown and beige adipocytes (brown-like adipocytes in white adipose tissue, WAT), and stimulating brown and beige adipocyte formation can be a new avenue to treat obesity. Angiotensin II (AngII) is a peptide hormone that plays important roles in energy metabolism via its angiotensin type 1 or type 2 receptors (AT1R and AT2R). Adipose tissue is a major source of AngII and expresses both types of its receptors, implying the autocrine and paracrine role of AngII in regulating adipose functions and self-remodeling. Here, based on the in vitro studies on primary cultures of mouse white adipocytes, we report that, AT2R activation, either by AngII or AT2R agonist (C21), induces white adipocyte browning, by increasing PPARγ expression, at least in part, via ERK1/2, PI3kinase/Akt and AMPK signaling pathways. It is also found that AngII–AT2R enhances brown adipogenesis. In the in vivo studies on mice, administration of AT1R antagonist (ZD7155) or AT2R agonist (C21) leads to the increase of WAT browning, body temperature and serum adiponectin, as well as the decrease of WAT mass and the serum levels of TNFα, triglycerides and free fatty acids. In addition, AT2R-induced browning effect is also observed in human white adipocytes, as evidenced by the increased UCP1 expression and oxygen consumption. Finally, we provide evidence that AT2R plays important roles in hormone T3-induced white adipose browning. This study, for the first time, reveals the browning and brown adipogenic effects of AT2R and suggests a potential therapeutic target to combat obesity and related metabolic disorders. Nature Publishing Group 2017-06-23 /pmc/articles/PMC5661636/ /pubmed/29263921 http://dx.doi.org/10.1038/sigtrans.2017.22 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
Than, Aung
Xu, Shaohai
Li, Ru
Leow, Melvin Khee-Shing
Sun, Lei
Chen, Peng
Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
title Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
title_full Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
title_fullStr Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
title_full_unstemmed Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
title_short Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
title_sort angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661636/
https://www.ncbi.nlm.nih.gov/pubmed/29263921
http://dx.doi.org/10.1038/sigtrans.2017.22
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