In order to elucidate the immune signaling pathways contributing to increased IAV-induced inflammation and lung injury in HFD mice, we investigated NF-κB signaling, Leptin-STAT3, oxidized phospholipids and TRAIL-mediated apoptosis, pathways known to play important roles in obesity-related pathologies. This evidence concerns the gene TNFSF10 and obesity due to melanocortin 4 receptor deficiency.