Neural substrate for an integrated metabolic control of feeding behavior

Evidence indicates that feeding behavior in rats is controlled by a mechani sm that integrates information about different aspects of fuel metabolism. We investigated the neural substrate for this integrated control by measuri ng the effect of metabolic inhibitors given alone and in combination on foo d intake and neuronal activity as reflected by the expression of c-Fos prot ein. Combined administration of methyl palmoxirate (5 mg/kg po), an inhibit or of fatty acid oxidation, and 2,5-anhydro-D-mannitol (150 mg/kg ip), whic h decreases liver ATP content, increased feeding in rats more than expected on the basis of eating responses after treatment with either inhibitor giv en alone. Combined treatment also produced a synergistic increase in Fos-li ke immunoreactivity in several brain areas, including the nucleus of the so litary tract, area postrema, and parvocellular portion of the hypothalamic paraventricular nucleus. These findings provide strong evidence for the inv olvement of selected brain regions in the metabolic control of food intake and suggest that metabolic information used to control feeding behavior is integrated in the periphery or at the level of the brain stem.