Maternal indole supplementation protects offspring from NAFLD through altered microbiota- and AHR-mediated ceramide metabolism

The relative importance of the AHR ligands Indole and Indole-3-acetate (I3A) to prevent WD-induced developmental programming of NAFLD in offspring is unknown. Although AHR signaling has been shown to regulate liver metabolism (e.g., lipids, xenobiotics, organic acids) and bioenergetics, little is known about the long-term protective effect in offspring exposed to maternal WD. In the current study, we investigate the effects of supplementation with Ind and I3A during obese pregnancy and lactation on re-programming offspring metabolism and liver health and identify new AHR- and microbial-mediated pathways conferring hepatoprotection in the next generation.