Notably, adipose tissue dysfunction in obesity creates an ’inflammatory reservoir’ via sustained IL‐6/TNF‐α secretion, which downregulates JAK‐STAT signaling pathways and reduces drug bioavailability [33, 39]—mechanistically explaining primary nonresponse to upadacitinib [36] and delayed dupilumab response in high SII‐IgE patients [38]. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.