Fig. 8: Schematic diagram of the mechanism underlying maternal HFD-induced offspring behavioral dysfunction.

Prenatal HFD enhanced maternal inflammatory activities, promoting the accumulation of Kyn metabolites in the maternal bloodstream. Most Kyn metabolites readily cross the blood-brain barrier. Concurrently, maternal HFD-associated MIA stimulated the overactivity of microglia within the fetal brain, culminating in the transformation of Kyn into the neurotoxic compound Quin. An overabundance of Quin subsequently induced an oxidative stress response, which impairs neuronal migration within the fetal neocortex and postnatal social behavioral phenotypes.