INS and obesity due to melanocortin 4 receptor deficiency: Insulin resistance is generally defined as an insufficient response to insulin by target cells (Konner and Bruning, 2012; Butterfield et al., 2014a) and represents a central feature of metabolic disorders, including T2DM and obesity (Lazar, 2005; Kahn et al., 2006; Bluher, 2016; Lin et al., 2016).