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Inhibition of CXXC5 function reverses obesity-related metabolic diseases
DC Field | Value | Language |
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dc.contributor.author | 이용호 | - |
dc.contributor.author | 한대훈 | - |
dc.date.accessioned | 2022-12-22T01:47:04Z | - |
dc.date.available | 2022-12-22T01:47:04Z | - |
dc.date.issued | 2022-04 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/191342 | - |
dc.description.abstract | Background: Metabolic diseases, including type 2 diabetes, have long been considered incurable, chronic conditions resulting from a variety of pathological conditions in obese patients. Growing evidence suggests the Wnt/β-catenin pathway is a major pathway in adipose tissue remodelling, pancreatic β-cell regeneration and energy expenditure through regulation of key metabolic target genes in various tissues. CXXC5-type zinc finger protein 5 (CXXC5) is identified negative feedback regulator of the Wnt/β-catenin pathway that functions via Dishevelled (Dvl) binding. Methods: Expression level of CXXC5 was characterised in clinical samples and diabetes-induced mice model. Diabetes-induced mice model was established by using high-fat diet (HFD). HFD-fed mice treated with KY19334, a small molecule inhibiting CXXC5-Dvl protein-protein interaction (PPI), was used to assess the role of CXXC5 in metabolic diseases. Results: Here, we show that CXXC5 is overexpressed with suppression of Wnt/β-catenin signalling in visceral adipose tissues of patients with obesity-related diabetes. Meanwhile, Cxxc5-/- mice fed an HFD exhibited resistance to metabolic dysregulation. KY19334 restores the lowered Wnt/β-catenin signalling and reverses metabolic abnormalities as observed in HFD-fed Cxxc5-/- mice. Administration of KY19334 on HFD-fed mice had a long-lasting glucose-controlling effect through remodelling of adipocytes and regeneration of pancreatic β-cells. Conclusion: Overall, the inhibition of CXXC5 function by small molecule-mediated interference of Dvl binding is a potential therapeutic strategy for the treatment of obesity-related diabetes. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Wiley | - |
dc.relation.isPartOf | CLINICAL AND TRANSLATIONAL MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adipocytes / metabolism | - |
dc.subject.MESH | Adipose Tissue / metabolism | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | DNA-Binding Proteins* / antagonists & inhibitors | - |
dc.subject.MESH | DNA-Binding Proteins* / metabolism | - |
dc.subject.MESH | Diabetes Mellitus, Type 2* / complications | - |
dc.subject.MESH | Diabetes Mellitus, Type 2* / drug therapy | - |
dc.subject.MESH | Diabetes Mellitus, Type 2* / genetics | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Obesity / complications | - |
dc.subject.MESH | Obesity / drug therapy | - |
dc.subject.MESH | Obesity / genetics | - |
dc.subject.MESH | Transcription Factors* / antagonists & inhibitors | - |
dc.subject.MESH | Transcription Factors* / metabolism | - |
dc.subject.MESH | Wnt Signaling Pathway | - |
dc.title | Inhibition of CXXC5 function reverses obesity-related metabolic diseases | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Seol Hwa Seo | - |
dc.contributor.googleauthor | Eunhwan Kim | - |
dc.contributor.googleauthor | Soung-Hoon Lee | - |
dc.contributor.googleauthor | Yong-Ho Lee | - |
dc.contributor.googleauthor | Dai Hoon Han | - |
dc.contributor.googleauthor | Hyesun Go | - |
dc.contributor.googleauthor | Je Kyung Seong | - |
dc.contributor.googleauthor | Kang-Yell Choi | - |
dc.identifier.doi | 10.1002/ctm2.742 | - |
dc.contributor.localId | A02989 | - |
dc.contributor.localId | A04273 | - |
dc.relation.journalcode | J04026 | - |
dc.identifier.eissn | 2001-1326 | - |
dc.identifier.pmid | 35384342 | - |
dc.subject.keyword | CXXC5 | - |
dc.subject.keyword | Wnt/β-catenin pathway | - |
dc.subject.keyword | adipose tissue remodelling | - |
dc.subject.keyword | metabolic diseases | - |
dc.subject.keyword | pancreatic β-cell regeneration | - |
dc.contributor.alternativeName | Lee, Yong Ho | - |
dc.contributor.affiliatedAuthor | 이용호 | - |
dc.contributor.affiliatedAuthor | 한대훈 | - |
dc.citation.volume | 12 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | e742 | - |
dc.identifier.bibliographicCitation | CLINICAL AND TRANSLATIONAL MEDICINE, Vol.12(4) : e742, 2022-04 | - |
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