Sakata T, Arase K, Fujimoto K, Kurata K, Fukagawa K, Fukushima M, Steffens A B, Oomura Y
Department of Internal Medicine I, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Brain Res. 1988 Nov 8;473(1):43-50. doi: 10.1016/0006-8993(88)90313-7.
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.
通过向大鼠第三脑室注入1种外源性和6种内源性衍生物，研究了短链有机酸对摄食行为、血糖和胰岛素影响的结构特异性。甘油酸（GEA）（1.0微摩尔）、3,4 - 二羟基丁酸γ - 内酯（3,4 - DB）和3,4,5 - 三羟基戊酸γ - 内酯（3,4,5 - TP）（2.50微摩尔）最多可在24小时内减少食物摄入量。这些酸降低了注入后第一餐的食量，但不影响第一餐的延迟时间、进食速度、饮水或活动。注入2,4 - 二羟基丁酸γ - 内酯（2,4 - DB）（1.25微摩尔）、2,4,5 - 三羟基戊酸γ - 内酯（2,4,5 - TP）和一种外源性化合物2,4,5,6 - 四羟基己酸γ - 内酯（2,4,5,6 - TH）（2.50微摩尔）会引发短暂的初始进食，且不一定伴有餐时饮水。同时活动增加。在这些有机酸中，3,4 - DB和2,4,5 - TP对摄食的影响最为显著。2.50微摩尔的3,4 - DB诱导血糖升高，而胰岛素不受影响；2.50微摩尔的2,4,5 - TP导致低血糖，胰岛素持续但无显著升高。结果表明，内源性有机酸的微小结构差异，特别是4 - 丁内酯内酯环上羟基的位置，可能通过向参与进食和饱腹感的神经元传递本质上相互对立的信号，在进食调节中起重要作用。
