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

doi:10.1016/j.isci.2023.106272

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^*

^*Corresponding author for this work

Department of Biomedical Sciences

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

6 Citations (Scopus)

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Abstract

Beige adipocytes are thermogenic with high expression of uncoupling protein 1in 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 (Smad4^iEC-KO) was achieved by using the Smad4^Floxp/floxp and Tie2^CreERT2 mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of Smad4^iEC-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. © 2023 The Author(s).

Original language	English
Article number	106272
Journal	iScience
Volume	26
Issue number	3
Online published	25 Feb 2023
DOIs	https://doi.org/10.1016/j.isci.2023.106272
Publication status	Published - 17 Mar 2023

Funding

This study was supported by the National Natural Science Foundation of China (NSFC) grant 32071145 and 81922078, Hong Kong Research Grant Council (RGC) grants 14105321 and 14109519 to Tian XY; NSFC grant 91939302, RGC grants SRFS2021-4S04, C4024-16W, 14109618 to Huang Y.

Research Keywords

Biological sciences
Cell biology
Molecular biology
Physiology

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This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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title = "Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice",

abstract = "Beige adipocytes are thermogenic with high expression of uncoupling protein 1in 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. {\textcopyright} 2023 The Author(s).",

keywords = "Biological sciences, Cell biology, Molecular biology, Physiology",

author = "Chenguang Wang and Yalan Wu and Yangxian Li and Yang Zhang and Fung, {Yee Lok} and Tong, {Ka Kui} and Lau, {Chi Wai} and Li Xiang and Kwan, {Kin Ming} and Li-Ru You and Yu Huang and Tian, {Xiao Yu}",

year = "2023",

month = mar,

day = "17",

doi = "10.1016/j.isci.2023.106272",

language = "English",

volume = "26",

number = "3",

}

TY - JOUR

T1 - Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice

AU - Wang, Chenguang

AU - Wu, Yalan

AU - Li, Yangxian

AU - Zhang, Yang

AU - Fung, Yee Lok

AU - Tong, Ka Kui

AU - Lau, Chi Wai

AU - Xiang, Li

AU - Kwan, Kin Ming

AU - You, Li-Ru

AU - Huang, Yu

AU - Tian, Xiao Yu

PY - 2023/3/17

Y1 - 2023/3/17

N2 - Beige adipocytes are thermogenic with high expression of uncoupling protein 1in 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. © 2023 The Author(s).

AB - Beige adipocytes are thermogenic with high expression of uncoupling protein 1in 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. © 2023 The Author(s).

KW - Biological sciences

KW - Cell biology

KW - Molecular biology

KW - Physiology

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85150871517&origin=recordpage

U2 - 10.1016/j.isci.2023.106272

DO - 10.1016/j.isci.2023.106272

M3 - RGC 21 - Publication in refereed journal

C2 - 36915676

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 3

M1 - 106272

ER -

Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice

Abstract

Funding

Research Keywords

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SRFS: Systemic Benefits of Physical Activity: Crosstalk between Organs on Signal Transduction from Mechano-stimulation to Metabolism

GRF: Suppression of Hippo Pathway Mediates Endothelial Dysfunction through Activating the BMP4-SMAD Axis in Metabolic Disorder

Cite this

Smad4-mediated angiogenesis facilitates the beiging of white adipose tissue in mice

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

Access Output

Other Access Options

Permanent Link

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Projects

SRFS: Systemic Benefits of Physical Activity: Crosstalk between Organs on Signal Transduction from Mechano-stimulation to Metabolism

GRF: Suppression of Hippo Pathway Mediates Endothelial Dysfunction through Activating the BMP4-SMAD Axis in Metabolic Disorder

Cite this