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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-10-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877819300870 |
| _version_ | 1818016166082248704 |
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| author | Wei Sun Xuemei Zhao Zhengqi Wang Yi Chu Liufeng Mao Shaoqiang Lin Xuefei Gao Yuna Song Xiaoyan Hui Shiqi Jia Shibing Tang Yong Xu Aimin Xu Kerry Loomes Cunchuan Wang Donghai Wu Tao Nie |
| author_facet | Wei Sun Xuemei Zhao Zhengqi Wang Yi Chu Liufeng Mao Shaoqiang Lin Xuefei Gao Yuna Song Xiaoyan Hui Shiqi Jia Shibing Tang Yong Xu Aimin Xu Kerry Loomes Cunchuan Wang Donghai Wu Tao Nie |
| author_sort | Wei Sun |
| collection | DOAJ |
| 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. Keywords: Tbx15, Adipocyte, Thermogenesis, Browning, Obesity |
| first_indexed | 2024-04-14T07:08:26Z |
| format | Article |
| id | doaj.art-9ed36a15024343a3b3925f453e0f3e15 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-14T07:08:26Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-9ed36a15024343a3b3925f453e0f3e152022-12-22T02:06:30ZengElsevierMolecular Metabolism2212-87782019-10-01284857Tbx15 is required for adipocyte browning induced by adrenergic signaling pathwayWei Sun0Xuemei Zhao1Zhengqi Wang2Yi Chu3Liufeng Mao4Shaoqiang Lin5Xuefei Gao6Yuna Song7Xiaoyan Hui8Shiqi Jia9Shibing Tang10Yong Xu11Aimin Xu12Kerry Loomes13Cunchuan Wang14Donghai Wu15Tao Nie16Key Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaKey Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Nonglinxi Road 19, Guangzhou, Guangdong, 510080, PR ChinaCentral Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou, 510630, ChinaKey Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaClinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Nonglinxi Road 19, Guangzhou, Guangdong, 510080, PR ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, ChinaClinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Nonglinxi Road 19, Guangzhou, Guangdong, 510080, PR ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, ChinaCentral Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou, 510630, ChinaKey Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaKey Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, ChinaSchool of Biological Sciences and Maurice Wilkins Centre, University of Auckland, Auckland, New ZealandCentral Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou, 510630, ChinaKey Laboratory of Regenerative Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China; Corresponding author. Guangzhou Medical University, Guangzhou, China.Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Nonglinxi Road 19, Guangzhou, Guangdong, 510080, PR China; Central Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China; Corresponding author. Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Nonglinxi Road 19, Guangzhou, Guangdong, 510080, PR China.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. Keywords: Tbx15, Adipocyte, Thermogenesis, Browning, Obesityhttp://www.sciencedirect.com/science/article/pii/S2212877819300870 |
| spellingShingle | Wei Sun Xuemei Zhao Zhengqi Wang Yi Chu Liufeng Mao Shaoqiang Lin Xuefei Gao Yuna Song Xiaoyan Hui Shiqi Jia Shibing Tang Yong Xu Aimin Xu Kerry Loomes Cunchuan Wang Donghai Wu Tao Nie Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway Molecular Metabolism |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2212877819300870 |
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