For example, immune defects such as increased systemic inflammation and/or reduced immune competence (Cani et al., 2009; Rummel et al., 2010; Lawrence et al., 2012), which are reported in genetic models of severe obesity [ob/ob (deficient for leptin) and db/db (deficient for functional leptin receptor) mice], are associated with increased hippocampal cytokine (IL-1β, IL-6, TNF-α) expression (Dinel et al., 2011, 2014; Erion et al., 2014). This evidence concerns the gene IL6 and obesity due to melanocortin 4 receptor deficiency.