303-OR: Maternal High-Fat Diet Alters the Gut Microbiota–Liver Circadian Rhythms and Results In Metabolic Dysfunction in Offspring

Abstract

Maternal high-fat diet (HF) disturbs the gut microbiota-liver interactions and induces negative effects in the offspring, but its impact on metabolic, gut microbial, and hepatic circadian rhythms in the offspring (F1) are unknown. Here, we tested whether maternal HF could disrupt the metabolic rhythm in the juvenile (postnatal day [PND] 28) and adult offspring (PND112). Metagenomics, transcriptome, and metabolomics throughout the gut microbiota-liver axis were used to investigate the mechanism underpinning metabolic changes in the juvenile offspring. eJTK_Cycle was applied to characterize rhythmic patterns. Both juvenile and adult offspring of HF dams exhibited deteriorated glucose tolerance (P < 0.05) and a gain of the rhythm of serum glucose level (Control [Ctr], adjP > 0.05; HF, adjP < 0.05). Maternal HF altered the compositional and functional circadian rhythms of gut microbiota in the juvenile offspring. The rhythm of capacity for gut microbial synthesis of the short-chain fatty acid acetate was significantly gained in the juvenile offspring of HF dams (Ctr, adjP > 0.05; HF, adjP < 0.05). Consistently, maternal HF induced a rhythm gain of serum and liver acetate in the juvenile offspring (Ctr, adjP > 0.05; HF, adjP < 0.05). Meanwhile, maternal HF resulted in a gain of the rhythm of hepatic G6pc (Ctr, adjP > 0.05; HF, adjP < 0.05), a marker of gluconeogenesis metabolism. G6pc rhythmic expression was significantly correlated with serum acetate (R = 0.58, P < 0.05) and liver acetate (R = 0.64, P < 0.05) in the juvenile offspring. Taken together, we show that maternal HF disrupted the metabolic rhythm and the gut microbiota-liver rhythms, increasing susceptibility to metabolic dysfunction in the offspring. Disclosure L.Ding: None. J.Liu: None. Q.Zhang: None. X.Xiao: None. Funding National Natural Science Foundation of China (81870579)