Maternal Betaine Supplementation Mitigates Maternal High Fat Diet-Induced NAFLD in Offspring Mice through Gut Microbiota

Abstract

Maternal betaine supplementation has been proven to alleviate non-alcoholic fatty liver disease (NAFLD) in offspring caused by maternal high-fat diet (MHFD). The gut-liver axis plays an important role in NAFLD pathogenesis. However, whether maternal betaine supplementation can alleviate NAFLD in offspring by the gut-liver axis is unknown. C57BL/6J mice were fed with high-fat diet for 4 weeks before mating, and supplemented with 1% betaine during pregnancy and lactation. After weaning, offspring mice were fed with standard diet to 10 weeks. Maternal betaine supplementation reduced hepatic triglyceride content and alleviated hepatic steatosis in offspring mice exposed to MHFD. Furthermore, the mRNA expression of PPARα, CPT1α and FATP2 was increased and TNFα was reduced by maternal betaine supplementation. Maternal betaine intake decreased the relative abundances of Proteobateria, Desulfovibrio and Ruminococcus, but increased the relative abundances of Bacteroides and Parabacteroides. Moreover, maternal betaine intake increased the concentrations of short-chain fatty acids (SCFAs), including acetic acid, butyric acid and valeric acid, in the feces. Gut microbiota and SCFAs were significantly correlated with hepatic triglyceride content and expression of the above genes. Maternal betaine intake had no effect on other gut microbiota-related metabolites (bile acid and trimethylamine-n-oxide). Altogether, maternal betaine supplementation ameliorated MHFD-induced NAFLD possibly through regulating gut microbiota and SCFAs in offspring mice.