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TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis

Author

Listed:
  • Sneha Damal Villivalam

    (University of California Berkeley)

  • Dongjoo You

    (University of California Berkeley)

  • Jinse Kim

    (University of California Berkeley)

  • Hee Woong Lim

    (University of Cincinnati)

  • Han Xiao

    (University of California Berkeley)

  • Pete-James H. Zushin

    (University of California Berkeley)

  • Yasuo Oguri

    (University of California)

  • Pouya Amin

    (University of California Berkeley)

  • Sona Kang

    (University of California Berkeley)

Abstract

It has been suggested that beige fat thermogenesis is tightly controlled by epigenetic regulators that sense environmental cues such as temperature. Here, we report that subcutaneous adipose expression of the DNA demethylase TET1 is suppressed by cold and other stimulators of beige adipocyte thermogenesis. TET1 acts as an autonomous repressor of key thermogenic genes, including Ucp1 and Ppargc1a, in beige adipocytes. Adipose-selective Tet1 knockout mice generated by using Fabp4-Cre improves cold tolerance and increases energy expenditure and protects against diet-induced obesity and insulin resistance. Moreover, the suppressive role of TET1 in the thermogenic gene regulation of beige adipocytes is largely DNA demethylase-independent. Rather, TET1 coordinates with HDAC1 to mediate the epigenetic changes to suppress thermogenic gene transcription. Taken together, TET1 is a potent beige-selective epigenetic breaker of the thermogenic gene program. Our findings may lead to a therapeutic strategy to increase energy expenditure in obesity and related metabolic disorders.

Suggested Citation

  • Sneha Damal Villivalam & Dongjoo You & Jinse Kim & Hee Woong Lim & Han Xiao & Pete-James H. Zushin & Yasuo Oguri & Pouya Amin & Sona Kang, 2020. "TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18054-y
    DOI: 10.1038/s41467-020-18054-y
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    Cited by:

    1. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Hongrui Wang & Liang Yu & Jin’e Wang & Yaqing Zhang & Mengchen Xu & Cheng Lv & Bing Cui & Mengmeng Yuan & Yu Zhang & Yupeng Yan & Rutai Hui & Yibo Wang, 2023. "SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Yangmian Yuan & Yu Fan & Yihao Zhou & Rong Qiu & Wei Kang & Yu Liu & Yuchen Chen & Chenyu Wang & Jiajian Shi & Chengyu Liu & Yangkai Li & Min Wu & Kun Huang & Yong Liu & Ling Zheng, 2023. "Linker histone variant H1.2 is a brake on white adipose tissue browning," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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