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Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway

OBJECTIVE: The T-box gene Tbx15 is abundantly expressed in adipose tissues, especially subcutaneous and brown fat. Although its expression is correlated with obesity, its precise biological role in adipose tissue is poorly understood in vivo. Here we investigated the function of Tbx15 in brown adipo...

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Autores principales: Sun, Wei, Zhao, Xuemei, Wang, Zhengqi, Chu, Yi, Mao, Liufeng, Lin, Shaoqiang, Gao, Xuefei, Song, Yuna, Hui, Xiaoyan, Jia, Shiqi, Tang, Shibing, Xu, Yong, Xu, Aimin, Loomes, Kerry, Wang, Cunchuan, Wu, Donghai, Nie, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822144/
https://www.ncbi.nlm.nih.gov/pubmed/31352005
http://dx.doi.org/10.1016/j.molmet.2019.07.004
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author Sun, Wei
Zhao, Xuemei
Wang, Zhengqi
Chu, Yi
Mao, Liufeng
Lin, Shaoqiang
Gao, Xuefei
Song, Yuna
Hui, Xiaoyan
Jia, Shiqi
Tang, Shibing
Xu, Yong
Xu, Aimin
Loomes, Kerry
Wang, Cunchuan
Wu, Donghai
Nie, Tao
author_facet Sun, Wei
Zhao, Xuemei
Wang, Zhengqi
Chu, Yi
Mao, Liufeng
Lin, Shaoqiang
Gao, Xuefei
Song, Yuna
Hui, Xiaoyan
Jia, Shiqi
Tang, Shibing
Xu, Yong
Xu, Aimin
Loomes, Kerry
Wang, Cunchuan
Wu, Donghai
Nie, Tao
author_sort Sun, Wei
collection PubMed
description OBJECTIVE: The T-box gene Tbx15 is abundantly expressed in adipose tissues, especially subcutaneous and brown fat. Although its expression is correlated with obesity, its precise biological role in adipose tissue is poorly understood in vivo. Here we investigated the function of Tbx15 in brown adipose thermogenesis and white adipose browning in vivo. METHODS: In the present study, we generated adipose-specific Tbx15 knockout (AKO) mice by crossing Tbx15 floxed mice with adiponectin-Cre mice to delineate Tbx15 function in adipose tissues. We systematically investigated the influence of Tbx15 on brown adipose thermogenesis and white adipose browning in mice, as well as the possible underlying molecular mechanism. RESULTS: Upon cold exposure, adipocyte browning in inguinal adipose tissue was significantly impaired in Tbx15 AKO mice. Furthermore, ablation of Tbx15 blocked adipocyte browning induced by β3 adrenergic agonist CL 316243, which did not appear to alter the expression of Tbx15. Analysis of DNA binding sites using chromatin-immunoprecipitation (ChIP) revealed that TBX15 bound directly to a key region in the Prdm16 promoter, indicating it regulates transcription of Prdm16, the master gene for adipocyte thermogenesis and browning. Compared to control mice, Tbx15 AKO mice displayed increased body weight gain and decreased whole body energy expenditure in response to high fat diets. CONCLUSION: Taken together, these findings suggest that Tbx15 regulates adipocyte browning and might be a potential target for the treatment of obesity.
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spelling pubmed-68221442019-11-04 Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway Sun, Wei Zhao, Xuemei Wang, Zhengqi Chu, Yi Mao, Liufeng Lin, Shaoqiang Gao, Xuefei Song, Yuna Hui, Xiaoyan Jia, Shiqi Tang, Shibing Xu, Yong Xu, Aimin Loomes, Kerry Wang, Cunchuan Wu, Donghai Nie, Tao Mol Metab Original Article OBJECTIVE: The T-box gene Tbx15 is abundantly expressed in adipose tissues, especially subcutaneous and brown fat. Although its expression is correlated with obesity, its precise biological role in adipose tissue is poorly understood in vivo. Here we investigated the function of Tbx15 in brown adipose thermogenesis and white adipose browning in vivo. METHODS: In the present study, we generated adipose-specific Tbx15 knockout (AKO) mice by crossing Tbx15 floxed mice with adiponectin-Cre mice to delineate Tbx15 function in adipose tissues. We systematically investigated the influence of Tbx15 on brown adipose thermogenesis and white adipose browning in mice, as well as the possible underlying molecular mechanism. RESULTS: Upon cold exposure, adipocyte browning in inguinal adipose tissue was significantly impaired in Tbx15 AKO mice. Furthermore, ablation of Tbx15 blocked adipocyte browning induced by β3 adrenergic agonist CL 316243, which did not appear to alter the expression of Tbx15. Analysis of DNA binding sites using chromatin-immunoprecipitation (ChIP) revealed that TBX15 bound directly to a key region in the Prdm16 promoter, indicating it regulates transcription of Prdm16, the master gene for adipocyte thermogenesis and browning. Compared to control mice, Tbx15 AKO mice displayed increased body weight gain and decreased whole body energy expenditure in response to high fat diets. CONCLUSION: Taken together, these findings suggest that Tbx15 regulates adipocyte browning and might be a potential target for the treatment of obesity. Elsevier 2019-07-05 /pmc/articles/PMC6822144/ /pubmed/31352005 http://dx.doi.org/10.1016/j.molmet.2019.07.004 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Sun, Wei
Zhao, Xuemei
Wang, Zhengqi
Chu, Yi
Mao, Liufeng
Lin, Shaoqiang
Gao, Xuefei
Song, Yuna
Hui, Xiaoyan
Jia, Shiqi
Tang, Shibing
Xu, Yong
Xu, Aimin
Loomes, Kerry
Wang, Cunchuan
Wu, Donghai
Nie, Tao
Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
title Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
title_full Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
title_fullStr Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
title_full_unstemmed Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
title_short Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
title_sort tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822144/
https://www.ncbi.nlm.nih.gov/pubmed/31352005
http://dx.doi.org/10.1016/j.molmet.2019.07.004
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