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.