In preclinical models bitter substances unequivocally have potent effects on upper GI functions, particularly the secretion of gut hormones, including CCK, GLP-1 and ghrelin, associated with reductions in food intake and body weight, and a reduction in postprandial blood glucose excursions, including in models of obesity and type 2 diabetes. The gene discussed is GHRL; the disease is obesity due to melanocortin 4 receptor deficiency.