Chemical and neuronal control of feeding motivation.

The sugar acids, 3,4-dihydroxybutanoic acid gamma-lactone, 2-buten-4-olide and 2,4,5-trihydroxy pentanoic acid gamma-lactone which were found in blood modulate feeding behavior of rats by modifying neuronal activity in the lateral hypothalamic area [LHA] and the ventromedial hypothalamic nucleus [VMH]. The former two act as satiety substances and the latter as a hunger substance. Detection of changes in the concentration of these sugar acids in the blood by glucoreceptor neurons in the VMH and glucose-sensitive neurons in the LHA is important in the regulation of feeding. A phasic increase in fibroblast growth factor [FGF] was found in the cerebrospinal fluid after feeding. Cerebroventricular application of acidic FGF suppresses food intake. Interleukin-1 beta and tumor necrosis factor which have a quite similar amino acid sequence as FGF also suppress feeding. The neuronal mechanism of satiety action of these polypeptides is the same as the sugar acids. The results indicate that these endogenous substances participate in the central regulation of feeding. Hierarchial organization of the endogenous chemical information processing system which is composed of the viscera, medulla, hypothalamus and the cortex is discussed.