Dietary fructose causes defective insulin signalling and ceramide accumulation in the liver that can be reversed by gut microbiota modulation

ABSTRACTObjective: The link between metabolic derangement of the gut–2013liver–visceral white adipose tissue (v-WAT) axis and gut microbiota was investigated.Methods: Rats were fed a fructose-rich diet and treated with an antibiotic mix. Inflammation was measured in portal plasma, ileum, liver, and v-WAT, while insulin signalling was analysed by measuring levels of phosphorylated kinase Akt. The function and oxidative status of hepatic mitochondria and caecal microbiota composition were also evaluated.Results: Ileal inflammation, increase in plasma transaminases, plasma peroxidised lipids, portal concentrations of tumour necrosis factor alpha, lipopolysaccharide, and non-esterified fatty acids, were induced by fructose and were reversed by antibiotic. The increased hepatic ceramide content, inflammation and decreased insulin signaling in liver and v-WAT induced by fructose was reversed by antibiotic. Antibiotic also blunted the increase in hepatic mitochondrial efficiency and oxidative damage of rats fed ...