TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis

Villivalam, Sneha Damal; You, Dongjoo; Kim, Jinse; Lim, Hee‐Woong; Han, Xiao; Zushin, Pete-James H.; Oguri, Yasuo; Amin, P. W.; Kang, Sona

doi:10.1038/s41467-020-18054-y

Cited by 40 publications

(36 citation statements)

References 70 publications

(100 reference statements)

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“…DNA demethylase ten-eleven translocation 1 (Tet1) inhibits the thermogenic function of BAT by suppressing the thermogenic gene, Hdac1. The expression of Tet1 is decreased with cold-induced browning of scWAT in mice, and the Tet1-KO in WAT showed enhanced thermogenic function in adipocytes as measured by the expression of the thermogenic genes including Ucp1 and Pgc1α [164].…”

Section: Epigenetic Regulation Of Brown and Beige Adipocytesmentioning

confidence: 98%

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Brandão

Poojari

Rabiee

2021

IJMS

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The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

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Section: Epigenetic Regulation Of Brown and Beige Adipocytesmentioning

confidence: 98%

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Brandão

Poojari

Rabiee

2021

IJMS

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“…TET1 knockout mice showed improved cold tolerance, increased energy expenditure, and suppression of diet-induced obesity and insulin resistance. Furthermore, the repressive role of TET1 in thermogenic gene regulation in brown adipocytes is largely independent of DNA demethylase but coordinates with the proto-oncogene histone deacetylase 1 (HDAC1) to mediate epigenetic changes to repress thermogenic gene transcription [ 66 ].…”

Section: Tet1 In Clinical Diseasementioning

confidence: 99%

Advances in the DNA methylation hydroxylase TET1

Liu

Xiong

et al. 2021

Biomark Res

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Background The ten-eleven translocation 1 (TET1) protein is a 5-methylcytosine hydroxylase that belongs to the TET protein family of human α-ketoglutarate oxygenases. TET1 recognizes and binds to regions of high genomic 5′-CpG-3′ dinucleotide density, such as CpG islands, initiates the DNA demethylation program, and maintains DNA methylation and demethylation balance to maintain genomic methylation homeostasis and achieve epigenetic regulation. This article reviews the recent research progress of TET1 in the mechanism of demethylation, stem cells and immunity, various malignant tumours and other clinical diseases. Conclusion TET1 acts as a key factor mediating demethylation, the mechanism of which still remains to be investigated in detail. TET1 is also critical in maintaining the differentiation pluripotency of embryonic stem cells and plays anti- or oncogenic roles in combination with different signalling pathways in different tumours. In certain tumours, its role is still controversial. In addition, the noncatalytic activity of TET1 has gradually attracted attention and has become a new direction of research in recent years.

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“…[ 9 ] A recent study suggests that Tet1 acts as a repressor of thermogenic genes in beige adipocytes in a DNA demethylase‐independent manner. [ 10 ] Thus, the role of Tet1 in lipid metabolism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress

Yuan

Liu

Chen

et al. 2021

Molecular Nutrition Food Res

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Scope DNA methylation contributes to obesity, but the role of the DNA demethylase ten‐eleven translocation protein 1 (Tet1) in obesity remains unclear. Vitamin C is a cofactor for the Tet family of proteins, but whether vitamin C can be used to treat obesity via Tet1 awaits clarification. Methods and Results Tet1+/+ and Tet1+/− mice are fed a high fat diet (HFD). Higher weight gain and more severe hepatic steatosis, accompanied by reduced 5‐hydromethylcytosine (5hmC) levels, are found in the white adipose tissue and liver of Tet1+/− mice. Accumulated lipids are observed in palmitic acid or oleic acid treated primary hepatocytes derived from Tet1+/− mice, which are rescued by Tet1 overexpression or vitamin C treatment. Bisulfite sequencing reveals higher DNA methylation levels on lipolysis related genes in the liver of Tet1+/− mice. Notably, oral intake of vitamin C normalizes DNA methylation levels, promotes lipolysis, and decreases obesity in HFD‐fed Tet1+/− mice. Conclusions The results reveal a novel function of Tet1 in obesity and provide a new mechanism for the beneficial role of vitamin C in metabolic diseases through enhanced Tet1 activity.

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TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis

Cited by 40 publications

References 70 publications

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Advances in the DNA methylation hydroxylase TET1

Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress

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