Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice
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
Affiliations
Chenguang Wang
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Yalan Wu
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Yangxian Li
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Yang Zhang
School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong 518107, China
Yee Lok Fung
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Ka Kui Tong
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Chi Wai Lau
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Li Xiang
School of Biomedical Sciences, Heart and Vascular Institute, The Chinese University of Hong Kong, Hong Kong SAR, China
Kin Ming Kwan
School of Life Science, State Key Laboratory of Agrobiotechnology (CUHK), Center for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong SAR, China
Li-Ru You
Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
Yu Huang
School 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 author
Xiao Yu Tian
School 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 author
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.
