WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice

Yuqin Wang; Xinzhi Li; Cenxi Liu; Liying Zhou; Lei Shi; Zhiguo Zhang; Long Chen; Ming Gao; Lanyue Gao; Yuanyuan Xu; He Huang; Jin Li; Zheng Chen

doi:10.1093/lifemeta/loac028

WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice

Yuqin Wang
, Xinzhi Li
, Cenxi Liu
, Liying Zhou
, Lei Shi
, Zhiguo Zhang
, Long Chen
, Ming Gao
, Lanyue Gao
, Yuanyuan Xu
, He Huang
, Jin Li
, Zheng Chen^*

^*Corresponding author for this work

School of Life Science and Technology, Harbin Institute of Technology
Fudan University
Jilin University
China Medical University

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determine the maturation of brown adipocytes during postnatal development are not fully understood. Here, we identify Wilms' tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to the whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.

Original language	English
Pages (from-to)	270-284
Number of pages	15
Journal	Life Metabolism
Volume	1
Issue number	3
DOIs	https://doi.org/10.1093/lifemeta/loac028
State	Published - 1 Dec 2022
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BAT
METTL3
PRDM16
WTAP
mA
postnatal development

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10.1093/lifemeta/loac028

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title = "WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice",

abstract = "Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determine the maturation of brown adipocytes during postnatal development are not fully understood. Here, we identify Wilms' tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to the whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.",

keywords = "BAT, METTL3, PRDM16, WTAP, mA, postnatal development",

author = "Yuqin Wang and Xinzhi Li and Cenxi Liu and Liying Zhou and Lei Shi and Zhiguo Zhang and Long Chen and Ming Gao and Lanyue Gao and Yuanyuan Xu and He Huang and Jin Li and Zheng Chen",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "10.1093/lifemeta/loac028",

language = "英语",

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TY - JOUR

T1 - WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice

AU - Wang, Yuqin

AU - Li, Xinzhi

AU - Liu, Cenxi

AU - Zhou, Liying

AU - Shi, Lei

AU - Zhang, Zhiguo

AU - Chen, Long

AU - Gao, Ming

AU - Gao, Lanyue

AU - Xu, Yuanyuan

AU - Huang, He

AU - Li, Jin

AU - Chen, Zheng

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determine the maturation of brown adipocytes during postnatal development are not fully understood. Here, we identify Wilms' tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to the whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.

AB - Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determine the maturation of brown adipocytes during postnatal development are not fully understood. Here, we identify Wilms' tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to the whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.

KW - BAT

KW - METTL3

KW - PRDM16

KW - WTAP

KW - mA

KW - postnatal development

UR - https://www.scopus.com/pages/publications/85141707877

U2 - 10.1093/lifemeta/loac028

DO - 10.1093/lifemeta/loac028

M3 - 文章

AN - SCOPUS:85141707877

SN - 2097-2555

VL - 1

SP - 270

EP - 284

JO - Life Metabolism

JF - Life Metabolism

IS - 3

ER -

WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice

Abstract

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Keywords

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