A rise in Proteobacteria is an indicator of gut-liver axis-mediated nonalcoholic fatty liver disease in high-fructose-fed adult mice

Current evidence suggests that high fructose intake results in gut dysbiosis, leading to endotoxemia and NAFLD onset. Thus, the hypothesis of the study was that an enhanced Proteobacteria proportion in the cecal microbiota could be the most prominent trigger of NAFLD through enhanced endotoxin (LPS) in adult high-fructose-fed C57BL/6 mice. Male C57BL/6 mice received a control diet (n = 10, C: 76% of energy as carbohydrates, 0% as fructose) or high-fructose diet (n = 10, HFRU: 76% of energy as carbohydrate, 50% as fructose) for 12 weeks. Outcomes included biochemical analyses, 16S rDNA PCR amplification, hepatic stereology, and RT-qPCR. The groups showed similar body masses during the whole experiment. However, the HFRU group showed greater water intake and blood pressure than the C group. The HFRU group showed a significantly lower amount of Bacteroidetes and a predominant rise in Proteobacteria, implying increased LPS. The HFRU group also showed enhanced de novo lipogenesis (Chrebp expression), while beta-oxidation was decreased (Ppar-alpha expression). These results agree with the deposition of fat droplets within hepatocytes and the enhanced hepatic triacylglycerol concentrations, as observed in the photomicrographs, where the HFRU group had a higher volume density of steatosis than the C group. Thus, we confirmed that a rise in the Proteobacteria phylum proportion was the most prominent alteration in gut-liver axis-induced hepatic steatosis in HFRU-fed C57BL/6 mice. Gut dysbiosis and fatty liver were observed even in the absence of overweight in this dietary adult mouse model.