PS, a physicochemical phenomenon, is physically controlled by solvent components,[1b] and metabolites are the abundant cellular components.[6] Interestingly, HFDs and metabolic syndromes such as obesity deregulate immunity,[7, 8] which is controlled by PS.[1, 5, 13, 14] These observations suggested that certain metabolites (particularly obesity‐related metabolites) might dissolve the PS such as the cGAS–DNA PS to attenuate immunity. Here, CGAS is linked to obesity due to melanocortin 4 receptor deficiency.