Novel Immuno-Metabolism Pathways to Combat Obesity and Insulin Resistance

Nutritional unbalance develops the obesity led to diabetes and accompanied by insulin resistance is being the epidemics of the 21st century. Inflammation of adipose tissue serves one notable pathway that is driving the development of dysfunctional metabolic state, leading to hyperglycaemia and other pathophysiology complications. Within the adipose tissue, a pivotal role in modulating interactions between adipocytes and immune cells, notably macrophages. Therefore, this intricate interplay presents a novel and promising therapeutic approach to combat obesity weight and diabetes.
Our Solution:
Utilizing a peptide derived from SVEP1, a crucial component of adipose cells, we have developed an innovative intervention targeting its receptor (integrin α9β1) expressed on immune cells. The developed peptide acts as a potent ligand, effectively inhibiting the interaction between SVEP1 and integrin α9β1. Through this mechanism, our innovation provides significant efficacy in addressing obesity-induced adipose dysfunction, insulin resistance leading to lower weight and inflammation and shift the proinflammatory macrophage activity.

Applications and Insights:
• The SVEP1-based peptide demonstrates specific binding to integrin α9β1, expressed in adipose tissue macrophages, suppresses the activation of macrophages and reduces the pro-inflammatory cytokine production.
• Local administration of the peptide in Diet-Induced Obese (DIO) mice improves glucose uptake and insulin sensitivity, hepatic function, reduced weight along with modulating macrophage to anti-inflammatory phenotype and thereby improve the adipose tissue metabolism.
Conclusion: We highlight the significant role of the immune metabolism pathways in obesity and insulin resistance. SVEP1-derived peptide was identified as a new molecule which is regulating macrophages in obesity, mitigating inflammation, and restoring glucose homeostasis. This project offers insights into metabolic and immune mediators in adipose tissue and sets the stage for therapeutic developments targeting adipose dysfunction.

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