Rapamycin alters the feeding preference for amino acids and sugar in female Drosophila

Pharmacological interventions targeting the aging process hold significant promise for improving the quality of life in the elderly and reducing healthcare costs. Rapamycin, in particular, has exhibited significant anti-aging and lifespan-extending effects across multiple model organisms. However, chronic rapamycin administration may also lead to various adverse reactions since it reshapes energy metabolism. Here, using Drosophila melanogaster as a model, we show that life-prolonging doses of rapamycin significantly modify animal feeding behavior. Long-term administration of rapamycin decreased protein preference in females while enhancing their sugar intake. Utilizing a chemically defined diet, we identified that changes in amino acid and sugar feeding preferences emerged as early as the second day of rapamycin treatment, preceding any detectable decline in fecundity. However, rapamycin-induced changes in macronutrient feeding preferences were not observed in males and sterile mutant females. Overall, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, which is influenced by both sex and reproductive status.