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유전체항상성연구단
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Loss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression

DC Field Value Language
dc.contributor.authorByun, S.-
dc.contributor.authorLee, C.H.-
dc.contributor.authorJeong, H.-
dc.contributor.authorKim, H.-
dc.contributor.authorKwon, H.M.-
dc.contributor.authorPark, S.-
dc.contributor.authorKyung Jae Myung-
dc.contributor.authorAn, J.-
dc.contributor.authorMyunggon Ko-
dc.date.accessioned2023-01-27T01:55:36Z-
dc.date.available2023-01-27T01:55:36Z-
dc.date.created2022-07-11-
dc.date.issued2022-06-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/12918-
dc.description.abstractβ-adrenergic receptor (β-AR) signaling plays predominant roles in modulating energy expenditure by triggering lipolysis and thermogenesis in adipose tissue, thereby conferring obesity resistance. Obesity is associated with diminished β3-adrenergic receptor (β3-AR) expression and decreased β-adrenergic responses, but the molecular mechanism coupling nutrient overload to catecholamine resistance remains poorly defined. Ten-eleven translocation (TET) proteins are dioxygenases that alter the methylation status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine and further oxidized derivatives. Here, we show that TET proteins are pivotal epigenetic suppressors of β3-AR expression in adipocytes, thereby attenuating the responsiveness to β-adrenergic stimulation. Deletion of all three Tet genes in adipocytes led to increased β3-AR expression and thereby enhanced the downstream β-adrenergic responses, including lipolysis, thermogenic gene induction, oxidative metabolism, and fat browning in vitro and in vivo. In mouse adipose tissues, Tet expression was elevated after mice ate a high-fat diet. Mice with adipose-specific ablation of all TET proteins maintained higher levels of β3-AR in both white and brown adipose tissues and remained sensitive to β-AR stimuli under high-fat diet challenge, leading to augmented energy expenditure and decreased fat accumulation. Consequently, they exhibited improved cold tolerance and were substantially protected from diet-induced obesity, inflammation, and metabolic complications, including insulin resistance and hyperlipidemia. Mechanistically, TET proteins directly repressed β3-AR transcription, mainly in an enzymatic activity-independent manner, and involved the recruitment of histone deacetylases to increase deacetylation of its promoter. Thus, the TET-histone deacetylase-β3-AR axis could be targeted to treat obesity and related metabolic diseases.-
dc.language영어-
dc.publisherNational Academy of Sciences-
dc.titleLoss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000854979800011-
dc.identifier.scopusid2-s2.0-85132684600-
dc.identifier.rimsid78456-
dc.contributor.affiliatedAuthorKyung Jae Myung-
dc.contributor.affiliatedAuthorMyunggon Ko-
dc.identifier.doi10.1073/pnas.2205626119-
dc.identifier.bibliographicCitationProceedings of the National Academy of Sciences of the United States of America, v.119, no.26-
dc.relation.isPartOfProceedings of the National Academy of Sciences of the United States of America-
dc.citation.titleProceedings of the National Academy of Sciences of the United States of America-
dc.citation.volume119-
dc.citation.number26-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaScience & Technology - Other Topics-
dc.relation.journalWebOfScienceCategoryMultidisciplinary Sciences-
dc.subject.keywordPlusIMPROVES INSULIN SENSITIVITY-
dc.subject.keywordPlusDIET-INDUCED OBESITY-
dc.subject.keywordPlusENERGY-EXPENDITURE-
dc.subject.keywordPlusBROWN ADIPOCYTES-
dc.subject.keywordPlusBETA(3)-ADRENERGIC RECEPTOR-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusOXIDATION-
dc.subject.keywordPlusTISSUE-
dc.subject.keywordPlusDIFFERENTIATION-
dc.subject.keywordPlusINFLAMMATION-
dc.subject.keywordAuthorcatecholamine resistance-
dc.subject.keywordAuthorHDACs-
dc.subject.keywordAuthorobesity-
dc.subject.keywordAuthorTET proteins-
dc.subject.keywordAuthorβ3-AR-
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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