In addition, in high-fat diet-induced obesity, overexpression of TBK1 and IKKε leads to phosphorylation of PDE3B, thereby reducing catecholamine-induced uncoupling protein 1 (UCP1)-mediated oxidative phosphorylation activation, which decreases energy expenditure; it also affects hormone-sensitive lipase activity via the PDE3B-cAMP-PKA pathway, reducing lipolysis and exacerbating energy imbalance 51. The gene discussed is UCP1; the disease is obesity due to melanocortin 4 receptor deficiency.