Independent of their role in acute immune responses, TBK1 and IKKε were shown to be induced in response to obesity-dependent inflammation and directly phosphorylate phosphodiesterase (PDE) 3B23, a major cyclic AMP (cAMP) hydrolyzing PDE isoform in adipocytes24. Here, IKBKE is linked to obesity due to melanocortin 4 receptor deficiency.