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Targeted SHP-1 Silencing Modulates the Macrophage Phenotype, Leading to Metabolic Improvement in Dietary Obese Mice

Chronic over-nutrition promotes adipocyte hypertrophy that creates inflammatory milieu leading to macrophage infiltration and their phenotypic switching during obesity. The SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has been identified as an important player in inflammatory disease...

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Detalles Bibliográficos
Autores principales: Sharma, Yadhu, Ahmad, Altaf, Yavvari, Prabhu Srinivas, Kumar Muwal, Sandeep, Bajaj, Avinash, Khan, Farah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526246/
https://www.ncbi.nlm.nih.gov/pubmed/31108319
http://dx.doi.org/10.1016/j.omtn.2019.04.020
Descripción
Sumario:Chronic over-nutrition promotes adipocyte hypertrophy that creates inflammatory milieu leading to macrophage infiltration and their phenotypic switching during obesity. The SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has been identified as an important player in inflammatory diseases involving macrophages. However, the role of SHP-1 in modulating the macrophage phenotype has not been elucidated yet. In the present work, we show that adipose tissue macrophage (ATM)-specific deletion of SHP-1 using glucan particle-loaded siRNA improves the metabolic phenotype in dietary obese insulin-resistant mice. The molecular mechanism involves AT remodeling via reducing crown-like structure formation and balancing the pro-inflammatory (M1) and anti-inflammatory macrophage (M2) population. Therefore, targeting ATM-specific SHP-1 using glucan-particle-loaded SHP-1 antagonists could be of immense therapeutic use for the treatment of obesity-associated insulin resistance.