Dietary macronutrient imbalances lead to compensatory changes in peripheral taste via independent signaling pathways

Food choice, in animals, has been known to change with internal nutritional state, and also with variable dietary conditions. To better characterize mechanisms of diet-induced plasticity of food preference in Drosophila melanogaster, we synthesized diets with macronutrient imbalances and examined how food choice and taste sensitivity were modified in flies that fed on these diets. We found that dietary macronutrient imbalances caused compensatory behavioral shifts in both sexes to increase preference for the macronutrient that was scant in the food source, and simultaneously reduce preference for the macronutrient that was enriched. Further analysis with females revealed analogous changes in sweet taste responses in labellar neurons, with increased sensitivity on sugar-reduced diet and decreased sensitivity on sugar-enriched diet. Interestingly, we found differences in the onset of changes in taste sensitivity and behavior, which occur over one to four days, in response to dietary sugar reduction or enrichment. To investigate molecular mechanisms responsible for diet-induced taste modulation, we used candidate gene and transcriptome analyses. Our results indicate that signaling via Dop2R is involved in increasing cellular and behavioral sensitivity to sugar as well as in decreasing behavioral sensitivity to amino acids upon dietary sugar reduction. On the other hand, cellular and behavioral sensitivity to sugar relies on dilp5 and a decrease in sugar preference following dietary sugar abundance was correlated with downregulation of dilp5. Together, our results suggest that feeding preference for sugar and amino acid can be modulated independently to facilitate food choice that accounts for prior dietary experience.

众所周知，动物的食物选择会随体内营养状态以及多变的膳食环境发生改变。为了更好地解析黑腹果蝇（Drosophila melanogaster）膳食诱导的食物偏好可塑性机制，我们合成了宏量营养素失衡的膳食，并观察了取食这些膳食的果蝇其食物选择与味觉敏感性的变化情况。我们发现，膳食宏量营养素失衡会使雌雄果蝇均产生补偿性行为转变：提升对食物来源中匮乏宏量营养素的偏好，同时降低对富集宏量营养素的偏好。针对雌性果蝇的进一步分析显示，其唇瓣神经元的甜味味觉反应也出现了类似变化：在低糖膳食喂养下味觉敏感性提升，而在高糖膳食喂养下则下降。值得注意的是，我们发现针对膳食糖含量降低或富集的味觉敏感性与行为变化，其启动时间存在差异，该变化过程可持续1至4天。为探究膳食诱导味觉调控的分子机制，我们采用了候选基因与转录组分析手段。我们的研究结果表明，在膳食糖含量降低时，通过Dop2R介导的信号通路参与提升细胞与行为对糖类的敏感性，同时降低对氨基酸的行为敏感性。另一方面，细胞与行为对糖类的敏感性依赖于dilp5；当膳食糖含量充足时，果蝇对糖类的偏好降低，这与dilp5的表达下调存在相关性。综上，我们的研究结果表明，果蝇对糖类与氨基酸的取食偏好可被独立调控，从而帮助其根据既往膳食经验调整食物选择。