Sharma, Yadhu and Ahmad, Altaf and Yavvari, Prabhu Srinivas and Kumar Muwal, Sandeep and Bajaj, Avinash and Khan, Farah (2019) Targeted SHP-1 Silencing Modulates the Macrophage Phenotype, Leading to Metabolic Improvement in Dietary Obese Mice. Molecular Therapy - Nucleic Acids, 16. pp. 626-636. ISSN 21622531

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Abstract

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.

Item Type:	Article
Subjects:	Biomedical Science Bioengineering & Devices Biochemical and Biophysical Sciences
Depositing User:	RCB Library
Date Deposited:	25 Jun 2020 07:40
Last Modified:	25 Jun 2020 07:40
URI:	http://rcb.sciencecentral.in/id/eprint/279

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