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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Main Authors: Than, Aung, Xu, Shaohai, Li, Ru, Leow, Melvin Khee-Shing, Sun, Lei, Chen, Peng
Other Authors: School of Chemical and Biomedical Engineering
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Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/147541
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spelling sg-ntu-dr.10356-1475412023-12-29T06:48:46Z 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 School of Chemical and Biomedical Engineering Science Browning White Adipose Tissue 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. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This work was supported by the Singapore National Research Foundation under its CBRG grant (NMRC/CBRG/0070/2014) and administrated by the Singapore Ministry of Health’s National Medical Research Council. 2021-04-06T02:26:31Z 2021-04-06T02:26:31Z 2017 Journal Article Than, A., Xu, S., Li, R., Leow, M. K., Sun, L. & Chen, P. (2017). Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis. Signal Transduction and Targeted Therapy, 2(1), 17022-. https://dx.doi.org/10.1038/sigtrans.2017.22 2059-3635 https://hdl.handle.net/10356/147541 10.1038/sigtrans.2017.22 29263921 2-s2.0-85051596190 1 2 17022 en Signal Transduction and Targeted Therapy © 2017 The Author(s). 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/ application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science
Browning
White Adipose Tissue
spellingShingle Science
Browning
White Adipose Tissue
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
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.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Than, Aung
Xu, Shaohai
Li, Ru
Leow, Melvin Khee-Shing
Sun, Lei
Chen, Peng
format Article
author Than, Aung
Xu, Shaohai
Li, Ru
Leow, Melvin Khee-Shing
Sun, Lei
Chen, Peng
author_sort Than, Aung
title 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_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_sort angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis
publishDate 2021
url https://hdl.handle.net/10356/147541
_version_ 1787136580190732288