C57Bl/6 mouse gut microbiome - HFCS

The rapid increase in obesity, diabetes and fatty liver disease in children over the past 20 years has been linked to increases in high fructose corn syrup (HFCS) consumption but mechanisms are unclear. Prior studies suggest that HFCS increases hepatic de novo lipogenesis. Given high rates of obesity and fatty liver disease in children and adolescents with high consumption of HFCS, it is essential to determine the effects of HFCS during this vulnerable developmental window and whether the effects are permanent. Therefore, we hypothesized that HFCS exposure during adolescence significantly impairs hepatic metabolic signaling pathways and alters gut microbial composition contributing to changes in energy metabolism. C57bl/6J mice were given free access to HFCS during adolescence (3-6 weeks of age) and underwent metabolic characterization at 6 and 30 weeks of age. At 6 weeks HFCS-exposed mice had significant increases in fat mass, glucose intolerance, hepatic triglycerides and de novo lipogenesis gene expression, with sex-specific effects. At 30 weeks changes in glucose tolerance and fat mass persisted in HFCS-exposed mice. Hepatic metabolomic studies showed enrichment of carbohydrate, amino acid, long chain fatty acid and secondary bile acid metabolism at 6 weeks with changes in secondary bile metabolism persisting in females at 30 weeks. Microbiome studies performed before and after HFCS exposure identified profound shifts of microbial species in male but not female mice. In summary, a short-term HFCS exposure during adolescence induces fatty liver, alters important metabolic pathways, some of which persist into adulthood, and changes the microbiome with sex-specific effects.