The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

Fructose, especially industrial fructose (sucrose and high fructose corn syrup) is commonly used in all kinds of beverages and processed foods. Liver is the primary organ for fructose metabolism, recent studies suggest that excessive fructose intake is a driving force in non-alcoholic fatty liver disease (NAFLD). Dietary fructose metabolism begins at the intestine, along with its metabolites, may influence gut barrier and microbiota community, and contribute to increased nutrient absorption and lipogenic substrates overflow to the liver. Overwhelming fructose and the gut microbiota-derived fructose metabolites (e.g., acetate, butyric acid, butyrate and propionate) trigger the de novo lipogenesis in the liver, and result in lipid accumulation and hepatic steatosis. Fructose also reprograms the metabolic phenotype of liver cells (hepatocytes, macrophages, NK cells, etc.), and induces the occurrence of inflammation in the liver. Besides, there is endogenous fructose production that expands the fructose pool. Considering the close association of fructose metabolism and NAFLD, the drug development that focuses on blocking the absorption and metabolism of fructose might be promising strategies for NAFLD. Here we provide a systematic discussion of the underlying mechanisms of dietary fructose in contributing to the development and progression of NAFLD, and suggest the possible targets to prevent the pathogenetic process.

Dietary fructose and risk of metabolic syndrome in Chinese residents aged 45 and above: results from the China National Nutrition and Health Survey

Background A growing number of researches supported that dietary fructose was associated with most of the key features of metabolic syndrome (MetS). However, there was no related epidemiological studies among Chinese population, despite the sharp increase in MetS cases. This study explores the relationship between dietary fructose and MetS among Chinese residents aged 45 and above. Methods A total of 25,528 participants (11,574 males and 13,954 females) were included in this nationwide representative cross-sectional study of China National Nutrition and Health Survey. Dietary fructose intake was assessed by 3-day 24-h dietary records. MetS was defined by the International Diabetes Federation and Chinese Diabetes Society criteria. Results The consumption of dietary fructose was 11.6 g/day for urban residents and 7.6 g/day for rural residents. Fruits and vegetables as well as their products were the main sources of fructose intake. There was no association between dietary fructose intake and the odds of having MetS in both urban (P = 0.315) and rural residents (P = 0.230) after adjustment for confounding factors. Moreover, for urban residents participating physical activities, the odds of having MetS in the fourth quartiles (OR: 0.67; 95%CI: 0.52-0.87) was lower than that in the first quartile. In the sensitivity analysis, a significant reduction in the odds of having MetS was also found in the fourth quartiles (OR, 95%CI: 0.68, 0.51-0.90; 0.67, 0.49-0.91; 0.74, 0.56-0.99) compared with the first quartile when excluding smokers, alcohol users, and underweight/obesity, respectively. And there was no association between dietary fructose intake and the odds of having MetS after multivariate adjustment stratified by gender, smoking and alcohol use. Conclusions Under the current dietary fructose intake status, there was no association between dietary fructose intake and the odds of having MetS among Chinese residents aged 45 and above. Physical activity and relatively low fructose intake may have a beneficial synergistic effect on MetS.

GLUT5 is a determinant of dietary fructose-mediated exacerbation of experimental colitis

The western diet has been suggested to contribute to the rising incidence of Inflammatory Bowel Diseases. This has led to the hypothesis that fructose, a component of the western diet, could play a role in the pathogenesis of Inflammatory Bowel Diseases. A high fructose diet is known to exacerbate experimental colitis. This study tested whether the expression of GLUT5, the fructose transporter, is a determinant of the severity of experimental colitis during elevated fructose consumption and whether ileal inflammation is associated with altered GLUT5 expression in Crohn's Disease. Studies in genetically engineered mice showed that in comparison to Glut5+/+ mice, feeding a 15 kcal% fructose diet to Glut5-/- mice led to worse dextran sodium sulfate (DSS)-induced colitis. This effect was associated with elevated levels of colonic fructose and a shift in the fecal microbiota in Glut5-/- mice. Importantly, treatment with broad-spectrum antibiotics protected against the worsening of colitis mediated by dietary fructose in Glut5-/- mice. Gene expression analysis revealed that GLUT5 levels are reduced in patients with Crohn's ileitis. Moreover, levels of GLUT5 negatively correlated with levels of pro-inflammatory mediators. Collectively, these results demonstrate that dietary constituent (fructose)-host gene (GLUT5) interactions can shape the colonic microbiota thereby impacting the severity of colitis.