2020,
Nature Communications.
DOI:
10.1038/s41467-020-18054-y
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
, Sona Kang
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.
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2022-10-31 09:48:00
李翛然:
#paper TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis doi: https://doi.org/10.1038/s41467-020-18054-y
关于TET1 ，文献报道Tumor suppressor应该是没有问题，做为重组蛋白治疗肿瘤，我接下来要调研一下临床上哪类肿瘤病人是否有TET1缺失的现象，由此来判断肿瘤是否在TET1不缺失的情况下不好生长，确定其临床价值，还有一个要考虑的是这2篇文章介绍的TET1压抑脂肪细胞热能量代谢，维他命C作用在TET1压制somatic cell reprogramming，这2个现象是否可能导致严重的副作用，限制TET1的剂量