Your browser doesn't support javascript.
loading
Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogenesis and prevent obesity.
Fang, Lu; Liu, Changjie; Jiang, Zong-Zhe; Wang, Mengxiao; Geng, Kang; Xu, Yangkai; Zhu, Yujie; Fu, Yiwen; Xue, Jing; Shan, Wenxin; Zhang, Qi; Chen, Jie; Chen, Jiahong; Zhao, Mingming; Guo, Yuxuan; Siu, K W Michael; Chen, Y Eugene; Xu, Yong; Liu, Donghui; Zheng, Lemin.
Afiliación
  • Fang L; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Liu C; Department of Blood Transfusion, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510000, Guangdong, China.
  • Jiang ZZ; Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
  • Wang M; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China.
  • Geng K; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Xu Y; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, 646000, Sichuan, China.
  • Zhu Y; Department of plastic and burns surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
  • Fu Y; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Xue J; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Shan W; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Zhang Q; Beijing Tiantan Hospital, China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Capital Medical University, 6 Tiantan Xili, Chongwen District, 100050, Beijing, China.
  • Chen J; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Chen J; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Zhao M; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Guo Y; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Siu KWM; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Beijing Key Laboratory of Cardiovascular Rece
  • Chen YE; The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Recep
  • Xu Y; Center for Mass Spectrometry Research and Clinical Application, Shandong Public Health Clinical Center Affiliated to Shandong University, Lishan Campus, 46 Lishan Road, Jinan, Shandong, China.
  • Liu D; Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON, N9B 3P4, Canada.
  • Zheng L; Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Signal Transduct Target Ther ; 9(1): 218, 2024 Aug 23.
Article en En | MEDLINE | ID: mdl-39174522
ABSTRACT
Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A1 / Adipocitos / PPAR gamma / Adipogénesis / Obesidad Límite: Animals / Humans Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A1 / Adipocitos / PPAR gamma / Adipogénesis / Obesidad Límite: Animals / Humans Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido