Consequently, to fully understand the pre-clinical metabolic deteriorations observed in overweight and obesity it is important to consider the role of elevated plasma triglyceride concentrations (Hassing et al., 2012; Yuan et al., 2007), in addition to the rise in glucose and insulin, in the pathophysiology of cardio-metabolic diseases, which are among the leading causes of mortality in developed countries (Bays et al., 2004; Ford, 2005; Higgins and Adeli, 2017). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.