TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis

Sneha Damal Villivalam, Dongjoo You, Jinse Kim, Hee Woong Lim, Han Xiao, Pete-James H. Zushin, Yasuo Oguri, Pouya Amin and Sona Kang ()
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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

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18054-y

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DOI: 10.1038/s41467-020-18054-y

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