Hepatic versus cerebral origin of stimulus for feeding induced by 2-deoxy-d-glucose in rats

Intravenous administration of 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glucose utilization, increased the food intake of rats. Infusions of glucose or mannose abolished this effect, whereas equimolar fructose solutions did not affect 2-DG-induced feeding. Similar results were obtained when 2-DG and the hexoses were administered into the hepatic portal vein. These findings suggest that 2-DG elicits feeding due to glucoprivation at a site that is inaccessible to fructose. This site is likely to be in the brain, not the liver, because all three sugars can nourish peripheral tissue but only fructose cannot penetrate the blood-brain barrier. Moreover, 2-DG-induced feeding was abolished by intravenous infusion of beta-hydroxybutyrate, a substrate that can be oxidized by brain and other tissues but not by the liver.