4.2. Lipid metabolism underlying the multi-generational effects
Lipid metabolism plays crucial roles in supporting reproduction and growth and regulating lifespan (Hansen et al., 2013). It is known that TG is hydrolyzed to NEFA by lipase and ATGL, and NEFA can be synthesized back to TG by GPAT (Figure 3(D)) (Pradhan et al., 2018; Srinivasan et al., 2008). Therefore, the opposite effects on the metabolites (between TG and NEFA) and enzymes (between lipase and ATGL, between ATGL and GPAT) demonstrated that DEHTP disturbed the overall lipid metabolism with potential biased directions. Moreover, NEFA can form FA-CoA by ACS, and FA-CoA can react to ACA by CPT, while ACA can re-form NEFA by ACC and FAS (Pradhan et al., 2018; Srinivasan et al., 2008). The correlation between ACA and ACS (and also CPT and ACC) and between ATGL and GPAT demonstrated that DEHTP significantly promoted the overall lipid metabolism. Especially, such promotion occurred at environmental levels of DEHTP (e.g., 0.008 mg/L), showing the potential of DEHTP as an environmental obesogen. Combining the apical and biochemical effects, the positive correlations supported the connection between energy supply and reproduction. Meanwhile, the negative correlations indicated that the energy supply was balanced and even allocated with preference towards reproduction instead of locomotion behavior.
Notably, there were significant mismatches between lipid metabolism and the apical responses (i.e., locomotion). Such mismatch can be resulted from other energy consuming responses. It was reported that oxidative stress and antioxidant investment are known to cost energy and may directly involve trade-offs with other life traits (e.g., growth) (Yu et al., 2018). The influences of DEHTP on oxidative stress and antioxidant responses had been demonstrated in the human body (Huang et al., 2020). The mismatch urged further studies on the energy budget and also multi-omic analysis (e.g., lipidomic and transcriptomic) to reveal the essential connections among various responses.