As a result, GABAB receptors are activated in nearby neurons decreasing their production of anorexigenic brain-derived neurotrophic factor (BDNF) which ultimately causes hyperphagia and obesity [28, 29] Thus, the hypothalamic molecular and cellular perturbations in response to chronic high-fat diet consumption are multifaceted, involving a complex array of signaling molecules and cell types originating both peripherally and centrally which act in tandem to disrupt whole-body energy balance regulation (Figure 3). This evidence concerns the gene BDNF and obesity due to melanocortin 4 receptor deficiency.