Full metadata record
DC Field | Value | Language |
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dc.citation.number | 26 | - |
dc.citation.startPage | e220562611 | - |
dc.citation.title | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.volume | 119 | - |
dc.contributor.author | Byun, Seongjun | - |
dc.contributor.author | Lee, Chan Hyeong | - |
dc.contributor.author | Jeong, Hyumgmin | - |
dc.contributor.author | Kim, Hyejin | - |
dc.contributor.author | Kwon, Hyug Moo | - |
dc.contributor.author | Park, Sung Ho | - |
dc.contributor.author | Myung, Kyungjae | - |
dc.contributor.author | An, Jungeun | - |
dc.contributor.author | Ko, Myunggon | - |
dc.date.accessioned | 2023-12-21T14:07:46Z | - |
dc.date.available | 2023-12-21T14:07:46Z | - |
dc.date.created | 2022-07-28 | - |
dc.date.issued | 2022-06 | - |
dc.description.abstract | β-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.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.119, no.26, pp.e220562611 | - |
dc.identifier.doi | 10.1073/pnas.2205626119 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.scopusid | 2-s2.0-85132684600 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/59043 | - |
dc.identifier.wosid | 000854979800011 | - |
dc.language | 영어 | - |
dc.publisher | National Academy of Sciences | - |
dc.title | Loss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression | - |
dc.type | Article | - |
dc.description.isOpenAccess | TRUE | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | catecholamine resistance | - |
dc.subject.keywordAuthor | HDACs | - |
dc.subject.keywordAuthor | obesity | - |
dc.subject.keywordAuthor | TET proteins | - |
dc.subject.keywordAuthor | β3-AR | - |
dc.subject.keywordPlus | IMPROVES INSULIN SENSITIVITY | - |
dc.subject.keywordPlus | DIET-INDUCED OBESITY | - |
dc.subject.keywordPlus | ENERGY-EXPENDITURE | - |
dc.subject.keywordPlus | BROWN ADIPOCYTES | - |
dc.subject.keywordPlus | BETA(3)-ADRENERGIC RECEPTOR | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | OXIDATION | - |
dc.subject.keywordPlus | TISSUE | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | INFLAMMATION | - |
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