Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice
Summary: Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that Smad4 is important for angiogenesis. Here we studied whether endothelial Smad4-mediated angiogenesis is involved in WAT...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223003498 |
| _version_ | 1811155477741961216 |
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| author | Chenguang Wang Yalan Wu Yangxian Li Yang Zhang Yee Lok Fung Ka Kui Tong Chi Wai Lau Li Xiang Kin Ming Kwan Li-Ru You Yu Huang Xiao Yu Tian |
| author_facet | Chenguang Wang Yalan Wu Yangxian Li Yang Zhang Yee Lok Fung Ka Kui Tong Chi Wai Lau Li Xiang Kin Ming Kwan Li-Ru You Yu Huang Xiao Yu Tian |
| author_sort | Chenguang Wang |
| collection | DOAJ |
| description | Summary: Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that Smad4 is important for angiogenesis. Here we studied whether endothelial Smad4-mediated angiogenesis is involved in WAT beiging. Inducible knockout of endothelial cell (EC) selective Smad4 (Smad4iEC-KO) was achieved by using the Smad4Floxp/floxp and Tie2CreERT2 mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of Smad4iEC-KO mice, with the less proliferation of ECs and adipogenic precursors. RNA sequencing of human ECs showed that Smad4 is involved in angiogenesis-related pathways. Knockdown of SMAD4 attenuated the upregulation of VEGFA, PDGFA, and angiogenesis in vitro. Treatment of human ECs with palmitic acid-induced Smad1/5 phosphorylation and the upregulation of core endothelial genes. Our study shows that endothelial Smad4 is involved in WAT beiging through angiogenesis and the expansion of adipose precursors into beige adipocytes. |
| first_indexed | 2024-04-10T04:34:48Z |
| format | Article |
| id | doaj.art-35b22b0f509546ea808cab8d3da53e52 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T04:34:48Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-35b22b0f509546ea808cab8d3da53e522023-03-10T04:35:50ZengElsevieriScience2589-00422023-03-01263106272Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in miceChenguang Wang0Yalan Wu1Yangxian Li2Yang Zhang3Yee Lok Fung4Ka Kui Tong5Chi Wai Lau6Li Xiang7Kin Ming Kwan8Li-Ru You9Yu Huang10Xiao Yu Tian11School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong 518107, ChinaSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, ChinaSchool of Life Science, State Key Laboratory of Agrobiotechnology (CUHK), Center for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong SAR, ChinaInstitute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, TaiwanSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong 518057, China; Corresponding authorSchool of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China; CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong 518057, China; Corresponding authorSummary: Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that Smad4 is important for angiogenesis. Here we studied whether endothelial Smad4-mediated angiogenesis is involved in WAT beiging. Inducible knockout of endothelial cell (EC) selective Smad4 (Smad4iEC-KO) was achieved by using the Smad4Floxp/floxp and Tie2CreERT2 mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of Smad4iEC-KO mice, with the less proliferation of ECs and adipogenic precursors. RNA sequencing of human ECs showed that Smad4 is involved in angiogenesis-related pathways. Knockdown of SMAD4 attenuated the upregulation of VEGFA, PDGFA, and angiogenesis in vitro. Treatment of human ECs with palmitic acid-induced Smad1/5 phosphorylation and the upregulation of core endothelial genes. Our study shows that endothelial Smad4 is involved in WAT beiging through angiogenesis and the expansion of adipose precursors into beige adipocytes.http://www.sciencedirect.com/science/article/pii/S2589004223003498Biological sciencesCell biologyMolecular biologyPhysiology |
| spellingShingle | Chenguang Wang Yalan Wu Yangxian Li Yang Zhang Yee Lok Fung Ka Kui Tong Chi Wai Lau Li Xiang Kin Ming Kwan Li-Ru You Yu Huang Xiao Yu Tian Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice iScience Biological sciences Cell biology Molecular biology Physiology |
| title | Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice |
| title_full | Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice |
| title_fullStr | Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice |
| title_full_unstemmed | Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice |
| title_short | Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice |
| title_sort | smad4 mediated angiogenesis facilitates the beiging of white adipose tissue in mice |
| topic | Biological sciences Cell biology Molecular biology Physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223003498 |
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