Stereospecific feeding modulation by endogenous organic acid gamma-lactone in rats

Stereospecificity of 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP) in their effects on feeding behavior and humoral factors was assessed by infusion into the rat third cerebroventricle. Initial transient food intake was most potently affected by infusion of 2.50 mumol of the 2S,4S-stereoisomer of 2,4,5-TP (80%) at 1100 h. Among the others, 2.50 mumol of the 2R,4S-isomer was somewhat potent in feeding elicitation (20%). Feeding induced by these isomers was not accompanied by periprandial drinking. Ambulation increased with elicitation of feeding. During the first dark period after infusion at 1940 h, 2.50 mumol of the 3S-isomer of 3,4-DB decreased food intake, including reduced meal size, and prolonged postprandial intermeal interval, but the 3R-isomer did not. Potent hypoglycemia with hyperinsulinemia was caused by the 2S,4S-isomer of 2,4,5-TP, and the S-isomer of 3,4-DB caused responses that were reciprocal to those to 2,4,5-TP. The remaining isomers did not affect feeding or humoral factors. The results suggest that the S- or S,S-stereo-isomer of the endogenous organic acid gamma-lactones may be important in modulating food intake through the hypothalamus.