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.