Structural and stereoisomeric specificity of serum-borne sugar acids related to feeding control by rats

Specificity of chemical structures and stereoisomers among serum-borne short-chain organic acids in rats were assessed for their effects on feeding behavior and humoral factors by infusion into the rat third cerebroventricle. Infusion of glyceric acid (1.0 mumol), 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) or 3,4,5-trihydroxypentanoic acid gamma-lactone (2.50 mumol) immediately before the dark phase decreased food intake for, at most, 24 h. These acids did not significantly affect drinking or ambulation. Initial feeding, not necessarily accompanied by periprandial drinking, was induced after infusion of 2,4-dihydroxybutanoic acid gamma-lactone, 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP) or exogenous 2,4,5,6-tetrahydroxyhexanoic acid gamma-lactone (2.50 mumol) in the light phase. Of these acids, 3,4-DB most potently suppressed and 2,4,5-TP most potently enhanced feeding. Of these, the 2S,4S-isomer and the 3S-isomer were the most potent of 2,4,5-TP and 3,4-DB, respectively. Only the 2S,4S-isomer of 2,4,5-TP induced hypoglycemia with hyperinsulinemia, whereas opposite effects were produced by the 3S-isomer of 3,4-DB. The results indicate that the positions of the hydroxyl groups on 4-butanolide and the S- and S,S-stereoisomers are important in modulating food intake through the hypothalamus.