Bitter taste and blood glucose are not involved in the suppressive effect of dietary histidine on food intake.

Abstract Histamine decreases food intake by activating histaminergic neurons in the hypothalamus. Histamine is synthesized by histidine decarboxylase (HDC) from histidine. The purpose of this three-part animal study was to clarify the mechanism underlying the suppressive effect of dietary histidine on food intake. In experiment 1, we attempted to distinguish palatability from a direct effect of dietary histidine because histidine tastes slightly bitter to humans. We measured food intake every hour for 24 h in rats fed with a histidine-enriched diet or one of various quinine diets (0.001–0.8% quinine), also bitter. In experiment 2, we measured changes in blood glucose levels in rats fed with a standard or histidine-enriched diet because blood glucose is known to decrease food intake. In experiment 3, we intraperitoneally injected fluoromethylhistidine (FMH), an antagonistic inhibitor of HDC, in rats fed with a histidine-enriched diet. In experiment 1, food intake was almost the same in rats fed with the histidine-enriched diet as that in rats fed with the 0.01% quinine diet until 6 h, but food intake was low in other groups compared with that in the histidine-enriched diet group. After 6 h, food intake did not increase in rats fed with the histidine-enriched diet. In experiment 2, the blood glucose level rose quickly and then began to decrease at approximately 2 h in both groups of rats. However, it decreased more dramatically in rats fed with the histamine-enriched diet and reaches a significant difference from the decrease in the standard-diet group by 6 h. In experiment 3, food intake increased significantly in FMH-injected rats fed with the histidine-enriched diet compared with in non-FMH injected rats. Our results suggest that dietary histidine suppresses food intake by activating histaminergic neurons in the hypothalamus, independently bitter taste and blood glucose level.