SUN-643 Potential Contributions of Gut Microbiota-Liver Axis to the Transgenerational Metabolic Reprogramming of Maternal Exercise

Background: Early-life overnutrition programs increased risks of metabolic disorders in adulthood. Regular exercise is widely accepted to be an effective measure to maintain metabolic health. However, the transgenerational effects of maternal exercise and the specific mechanism are largely unclear. Aims: Our objective was to investigate whether maternal exercise could alleviate the metabolic disturbances induced by early-life overnutrition in both dams and offspring and to explore the role of gut microbiota-liver axis in mediating the transgenerational metabolic reprogramming. Methods: C57BL/6 females were randomly divided into three groups 3 weeks before mating and during pregnancy: the control group, high-fat group, and high-fat with exercise group (voluntary wheel running training). They received their original diets during lactation. The male offspring had ad libitum access to chow diet from weaning to 24 weeks of age. Glucose tolerance test and serum biochemical parameters were detected. The cecal contents from dams at weaning and 8-week and 24 week of offspring were collected for 16s rDNA sequencing. Hepatic HE staining and transcriptome were performed in adult offspring. Results: The results showed that perinatal high-fat diet resulted in significant glucose intolerance, insulin resistance and lipid profiles disorders in both dams and offspring. Maternal exercise markedly improved insulin sensitivity in dams and metabolic disorders in offspring from young into adulthood, especially the hepatic steatosis. The decrease in harmful bacteria and the persistent enrichment of short chain fatty acid producers from mothers to adult offspring, particularly the genus Odoribacter, were all associated with improvement in metabolism by maternal exercise. In addition, maternal exercise significant upregulated FGF21 and genes involved in the fatty acid oxidation and TCA cycle in adult offspring, which were down-regulated by perinatal high-fat diet and were significantly correlated with the altered microbial species. Conclusion: Overall, maternal exercise could significantly mitigate the detrimental effects of perinatal high-fat diet on metabolism in both dams and male offspring. The continuous alterations in gut microbiota and reprogramming hepatic metabolism might be critical factors in deciphering the transgenerational metabolic benefits of maternal exercise, which provides some novel evidence and targets for combating the metabolic diseases.