Structural specificity among short-chain organic
acids for effects on feeding behavior,
blood glucose and
insulin was investigated by infusion of 1 exogenous and 6 endogenous derivatives into the rat third cerebral ventricle.
Glyceric acid (GEA) (1.0 mumol),
3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 3,4,5-trihydroxypentanoic
acid gamma-
lactone (3,4,5-TP) (2.50 mumol) decreased food intake for, at most, 24 h. These
acids depressed the size of the first meal after infusion, but did not affect latency to the first meal, eating speed, drinking or ambulation. Infusion of 2,4-dihydroxybutanoic
acid gamma-
lactone (2,4-DB) (1.25 mumol),
2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP), and an exogenous compound, 2,4,5,6-tetrahydroxyhexanoic
acid gamma-
lactone (2,4,5,6-TH) (2.50 mumol), induced transient initial feeding which was not necessarily accompanied by periprandial drinking. Ambulation was concomitantly increased. Of these organic
acids, 3,4-DB and
2,4,5-TP were most potent in their effects on feeding.
Hyperglycemia was induced by 2.50 mumol 3,4-DB leaving
insulin unaffected; 2.50 mumol
2,4,5-TP caused
hypoglycemia, with a persistent but not significant rise in
insulin. The results suggest that slight structural differences of endogenous organic
acids, in particular the positions of
hydroxyl groups on the
lactone ring of 4-butanolide, may be important in feeding modulation by conveying intrinsically reciprocal signals to neurons involved in feeding and satiety.