Chronic tetracycline exposure resulted in VPS13 dysregulation, lipid accumulation, and physiological impairments in Drosophila melanogaster

Antibiotics are widely detected in the environment due to their extensive use in medicine, aquaculture, and animal husbandry. Among these, tetracycline (TC) is recognized as a significant environmental contaminant with considerable ecological and public health implications. Continuous exposure to TC through contaminated food, water, and soil can lead to the accumulation of TC residues in the body, potentially exerting adverse effects on human health. To evaluate these effects, we used Drosophila melanogaster as a model organism. Our findings demonstrated that chronic exposure to TC at 1 mg/ml disrupted both metabolic and endocrine homeostasis as indicated by altered prothoracic gland morphology, reduced expression of ecdysone biosynthetic genes spo, phm, and dib, and significantly decreased 20-hydroxyecdysone levels. These changes were associated with developmental delay and reduced fecundity. TC exposure also increased lipid droplet accumulation, elevated TAG and glucose levels, shortened lifespan, and impaired locomotion. In addition, TC-treated flies exhibited reduced VPS13 expression, mitochondrial fragmentation, increased expression of Drp1, Pink1, Parkin, and Atg8a, enhanced oxidative stress, diminished antioxidant defences, and increased apoptosis. Molecular docking and molecular dynamics simulations further suggested a potential interaction between TC and the lipid-binding region of VPS13. Collectively, these findings indicate that chronic TC exposure is associated with altered lipid and endocrine homeostasis, mitochondrial dysfunction, oxidative stress, and impaired physiological performance in D. melanogaster. The observed reduction in VPS13 expression, together with the computational interaction analyses, suggests that VPS13 may contribute to the biological responses associated with TC exposure; however, further experimental studies are required to establish a direct mechanistic relationship.