Rhythm- and sex-dependent lipid accumulation in Drosophila melanogaster by phthalates

Phthalates (PAEs) have been linked to obesity prevalence. Their obesogenic effects were influenced by sexes and rhythm, while the underlying mechanisms remained to be explored. In the present study, dimethyl phthalate (DMP), dioctyl phthalate (DOP), diisopentyl phthalate (DIPP) and diisodecyl phthalate (DIDP) were chosen as the PAEs' representatives, and their obesogenic effects were measured in Drosophila melanogaster with consideration on sleep and eclosion rhythms and sex-dependent differences. Results showed that DMP and DOP stimulated body weight, and 4 PAEs commonly influenced the total sleep with less inhibition or more stimulation in males than in females. Biochemical analysis showed that 4 PAEs commonly elevated levels of triglyceride (TG), glucose and lactate with more significant effects in males than in females, with simultaneous more stimulated enzymes in males. Meanwhile, their stimulatory effects on cholesterol and pyruvate were more overwhelmed in females. In addition, the PAEs' effects on TG were more convincing in adults eclosed in afternoon (PM) than those in morning (AM), while their effects on glucose, lactate, cholesterol and pyruvate were more convincing in AM adults with simultaneous more stimulated enzymes than in PM ones. Further analysis on the expressions of the pdk-1/akt/foxo signaling pathway, and the results demonstrated that the PAEs' effects on lipid metabolism connected with their influences on rhythm and hormone regulations. The correlation analysis on the overall results demonstrated that the PAEs' toxicities were also influenced by the molecular weights.