Abstract
Background. Dopamine and serotonin (5-hydroxytryptamine, 5-HT) are versatile biogenic amines implicated in various physiological functions, notably in the regulation of metabolism. In mammals, their involvement in energy homeostasis is well documented. Objective. While the central roles of dopamine and serotonin are well characterized, their peripheral metabolic functions in invertebrates remain less defined. Therefore, we aimed to explore their involvement in lipid metabolism regulation in Drosophila melanogaster. Methods. Levels of carbohydrates, proteins, and lipids were quantified through spectrophotometric assays. Immunohistochemistry combined with confocal microscopy was used to assess expression patterns. Lipid droplets were stained using Nile Red to visualize lipid accumulation. Results. Loss-of-function mutants for 5-HT7 exhibit significantly elevated triacylglycerol (TAG) levels and enlarged lipid droplets, indicating disrupted lipid homeostasis. Expression analysis shows that 5-HT7 is broadly expressed in the brain, gut, and fat body—key metabolic organs—suggesting a role in systemic metabolic signaling. Targeted knockdown of 5-HT7 in the fat body recapitulates the lipid accumulation phenotype, supporting a tissue-autonomous function in lipid regulation. Notably, dietary supplementation with metformin restores TAG levels in 5-HT7 mutants, implicating energy-sensing pathways as potential downstream effectors of serotonergic metabolic control. Conclusion. The serotonin receptor 5-HT7 functions as a central regulator of lipid storage and underscores serotonin’s broader role in inter-organ metabolic coordination, with potential implications for understanding energy homeostasis in higher organisms.
