Upregulated GABAergic signalling during weight gain is consistent with previous reports that whilst NPY and/or AgRP gene deficiency is insufficient to reduce food intake [101], ablation of NPY/AgRP/GABA neurons results in acute hypophagia [102] and deletion of vesicular GABA transporter in AgRP neurons (which co-express NPY) results in a lean, obesity-resistant phenotype in mice [103]. This evidence concerns the gene NPY and obesity due to melanocortin 4 receptor deficiency.