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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：已证明膳食果糖摄入增加会产生多种有害的代谢作用，并有助于非酒精性脂肪性肝病（NAFLD）的发病机理。在患有肥胖和2型糖尿病的受试者中已经发现果糖载体葡萄糖转运蛋白-5(GLUT-5)和葡萄糖转运蛋白-2(GLUT-2)的肠道丰度增加。在这里，我们调查了GLUT-5和GLUT-2的肠道水平是否升高，导致更高的膳食果糖摄取，与NAFLD及其严重程度相关。
方法：对31例接受上消化道内镜检查的患者进行十二指肠粘膜活检，根据超声定义的NAFLD存在情况分为2组，对GLUT-5和GLUT-2蛋白水平进行评估。
结果：与没有NAFLD的人相比，患有NAFLD的人表现出十二指肠GLUT-5蛋白水平升高，独立于人口统计学和人体测量学混杂因素。相反，两组十二指肠GLUT-2丰度无差异.单因素相关分析显示GLUT-5蛋白水平与体重指数呈正相关,腰围,空腹和负荷后2小时胰岛素浓度，通过稳态模型评估IR（r=0.44；p=0.02）和肝脏IR（r=0.46；p=0.03）指标来估计胰岛素抵抗（IR）程度。此外，十二指肠GLUT-5丰度与血尿酸浓度呈正相关(r=0.40;p=0.05),与NAFLD进展有关的果糖代谢产物。重要的是,十二指肠GLUT-5水平与NAFLD纤维化评分估计的肝纤维化风险呈正相关.
结论：十二指肠GLUT-5水平升高与NAFLD和肝纤维化相关。肠GLUT-5介导的果糖摄取的抑制可以代表预防和治疗NAFLD的策略。
方法：对31例接受上消化道内镜检查的患者进行十二指肠粘膜活检，根据超声定义的NAFLD存在情况分为2组，对GLUT-5和GLUT-2蛋白水平进行评估。
结果：与没有NAFLD的人相比，患有NAFLD的人表现出十二指肠GLUT-5蛋白水平升高，独立于人口统计学和人体测量学混杂因素。相反，两组十二指肠GLUT-2丰度无差异.单因素相关分析显示GLUT-5蛋白水平与体重指数呈正相关,腰围,空腹和负荷后2小时胰岛素浓度，通过稳态模型评估IR（r=0.44；p=0.02）和肝脏IR（r=0.46；p=0.03）指标来估计胰岛素抵抗（IR）程度。此外，十二指肠GLUT-5丰度与血尿酸浓度呈正相关(r=0.40;p=0.05),与NAFLD进展有关的果糖代谢产物。重要的是,十二指肠GLUT-5水平与NAFLD纤维化评分估计的肝纤维化风险呈正相关.
结论：十二指肠GLUT-5水平升高与NAFLD和肝纤维化相关。肠GLUT-5介导的果糖摄取的抑制可以代表预防和治疗NAFLD的策略。
