● Knockout of Ikkε gene promotes improvement of whole-body metabolic status by decreasing the inflammatory cytokines expression and increasing the energy drainage. This also alters the expression of glucose- and lipid-metabolizing enzymes. ● As the absence of IKKε resolves the obesity-linked metabolic complications associated with insulin resistance and T2D, it can be used as therapeutic target for recovery in future. This evidence concerns the gene IKBKE and obesity due to melanocortin 4 receptor deficiency.