SVEP1-based peptide as a potential therapeutic agent against adipose tissue dysfunction and obesity

Adipose tissue dysfunction lies at the center of obesity pathogenesis. It is associated with surpassing the storage capacity of adipose cells, which leads to metabolic impairment and systemic meta-inflammation. Proteins involved in this process have drawn much attention due to their ability to affect the inflammatory response and alter the metabolic state. In this study, we identified SVEP1 and its receptor, integrin a9b1, as potential metabolic and immune regulators of adipose tissues and identified an SVEP1-based peptide as a possible therapeutic agent against adipose tissue dysfunction and obesity. Both proteins were upregulated in HFD-fed mice, and integrin was expressed in specific pro-inflammatory macrophage subpopulations. We generated a peptide based on the SVEP1 and characterized its binding properties. In-vitro accumulation assay indicated time and dose-dependent binding properties, while in vivo assays showed a specific binding capacity to immune subpopulations in adipose tissue. Our results, using the peptide, showed significant inhibition of migration and adhesion in macrophage-like cells. The peptide also affected the activation of the cells as co-incubation of the peptide with activated cells resulted in reduced nitrite production and inflammatory maker`s expression levels. Ex vivo tissues exhibited lower inflammation levels in adipose tissue macrophages, and in vivo adipose-treated tissues had a favorable metabolic state. This study will provide a valuable opportunity to advance the understanding of potential metabolic and immune mediators in adipose tissue and other tissues and can serve as the foundation for future therapeutics