Peripheral Neuropeptide Signaling
Peripheral Neuropeptide Signaling
This project explores the role of the immune-derived opioid peptide nociceptin/orphanin FQ (N/OFQ), encoded by the Pnoc gene and produced by B cells, in the development of obesity-associated metabolic dysfunction. Through genetic and molecular approaches, our study demonstrates that conditional deletion of Pnoc in B cells (PnocΔCD19) mitigates obesity-associated inflammation and improves systemic metabolic health.
Key findings show that PnocΔCD19 mice exhibit reduced macrophage infiltration and inflammatory gene expression in both adipose tissue and the liver under high-fat diet (HFD) conditions. These mice also display improved glucose tolerance and enhanced insulin sensitivity without changes in overall body weight or energy expenditure. Mechanistic studies reveal that N/OFQ enhances macrophage migration and promotes a pro-inflammatory metabolic state through its receptor, NOP. Notably, the deletion of Pnoc in B cells alters the adipose tissue secretome, reducing the recruitment of macrophages and other immune cells that contribute to metabolic inflammation.
By identifying the N/OFQ-NOP signaling axis as a driver of metabolic inflammation, this research provides a foundation for targeting this pathway in the development of novel therapeutic interventions for obesity-related disorders, including insulin resistance and type 2 diabetes.