Our data support a study by Sakar et al. who proposed a positive regulatory control loop between a high-fructose diet and intestinal GLUT2/GLUT5 transporters which is at the same time linked to hepatic metabolic Org 12962 hydrochloride functions in rodents. As expected, liver to body weight ratio is increased in all the high-sugar diet fed mice compared to control mice, which is in agreement with the increased overall hepatic lipid accumulation we see in liver tissue. Similar to mice fed a high-sugar diet, obese subjects have elevated small intestinal GLUT2 and GLUT5 levels in contrast to lean subjects. Of course, we cannot say that sugars lead to the effects we show in obese humans, but we assume that the excessive consumption of a westerns style diet in the obese group might have an influence on the here shown dysregulation of weight regulating parameters. Underlining our statement, it is clearly shown in the literature, that obese have a greater energy intake than expenditure. In contrast, lean humans in general have a balanced energy household. Nevertheless, we have to keep in mind that some studies show no increase in overall dietary carbohydrate uptake in overweight/obese compared to lean subjects. Therefore, it is of importance to calculate the absorbed or metabolisable energy meaning the difference between gross energy in consumed food and energy in feces and urine. We here use values from the literature referring to Southgate and Durnin who showed that with bomb NVP 231 calorimetry determined and on the other hand calculated values are in good agreement. Another report using a rodent model showed that Atwater factors predicted metabolisable energy with satisfactory accuracy in purified diets as we used here. However, it is of note, that data available for our article was measured in humans or chicken. Interestingly, small intestinal CCK is down-regulated in obese compared to lean humans. Our finding suggests a CCK dysregulation that might lead to reduced satiety signaling, boosting the development of obesity. In conclusion, our data indicates that liquid high-sugar diets compared to solid high-sugar diets differentially modulate feeding behavior, as well as intestinal sugar transporters, and hormone expression. Our study implicates a risk for an increased consumption of sucrose sweetened beverages, followed by elevated intestinal energy uptake and the development of fatty liver disease. According to the data we present here, antagonists of GLUT2 and GLUT5 might be novel pharmacologic targets for modulating feeding behavior and intestinal sugar uptake in obese patients. GLUT2 and GLUT5 inhibitors could prevent from a dramatically increased intestinal sugar uptake, presumably leading to weight reduction.