Association between higher duodenal levels of the fructose carrier glucose transporter-5 and nonalcoholic fatty liver disease and liver fibrosis.

ABSTRACT

BACKGROUND: An increased dietary fructose intake has been shown to exert several detrimental metabolic effects and contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). An augmented intestinal abundance of the fructose carriers glucose transporter-5 (GLUT-5) and glucose transporter-2 (GLUT-2) has been found in subjects with obesity and type 2 diabetes. Herein, we investigated whether elevated intestinal levels of GLUT-5 and GLUT-2, resulting in a higher dietary fructose uptake, are associated with NAFLD and its severity. METHODS: GLUT-5 and GLUT-2 protein levels were assessed on duodenal mucosa biopsies of 31 subjects divided into 2 groups based on ultrasound-defined NAFLD presence who underwent an upper gastrointestinal endoscopy. RESULTS: Individuals with NAFLD exhibited increased duodenal GLUT-5 protein levels in comparison to those without NAFLD, independently of demographic and anthropometric confounders. Conversely, no difference in duodenal GLUT-2 abundance was observed amongst the two groups. Univariate correlation analyses showed that GLUT-5 protein levels were positively related with body mass index, waist circumference, fasting and 2 h post-load insulin concentrations, and insulin resistance (IR) degree estimated by homeostatic model assessment of IR (r = 0.44; p = 0.02) and liver IR (r = 0.46; p = 0.03) indexes. Furthermore, a positive relationship was observed between duodenal GLUT-5 abundance and serum uric acid concentrations (r = 0.40; p = 0.05), a product of fructose metabolism implicated in NAFLD progression. Importantly, duodenal levels of GLUT-5 were positively associated with liver fibrosis risk estimated by NAFLD fibrosis score. CONCLUSION: Increased duodenal GLUT-5 levels are associated with NAFLD and liver fibrosis. Inhibition of intestinal GLUT-5-mediated fructose uptake may represent a strategy for prevention and treatment of NAFLD.