Nociceptin-mediated immune signaling promotes obesity-associated metabolic dysfunction
We are exploring how immune-derived opioid peptides regulate metabolism, focusing on a newly identified immunometabolic pathway that connects immune system activity to energy balance and insulin sensitivity. By targeting this pathway with novel opioid receptor antagonists, we aim to reduce chronic inflammation and restore metabolic health in obesity.
Scientists working in the project
Publications
2025 iScience
Immune-derived opioid peptides have been implicated in immune regulation and inflammatory processes. Here, we investigate the effects of nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in obesity. Selectively targeting N/OFQ, encoded by the Pnoc gene, in B cells mitigates the adverse metabolic effects of diet-induced obesity and enhances insulin sensitivity and glucose tolerance. Notably, B cell-specific Pnoc knockout mice display a marked reduction in markers of immune cell migration and diminished macrophage recruitment in adipose tissue and liver. Mechanistically, we identify that N/OFQ promotes macrophage recruitment and metabolic inflammation, exacerbating glucose intolerance and insulin resistance during obesity. Overall, the immunomodulatory properties exhibited by the N/OFQ-NOP system render it a promising therapeutic target for mitigating metabolic inflammation.