4. Discussion
weight loss
It has previously been shown that macronutrient quality (i.e., GI of carbohydrates and saturation of fats) can influence liver fat storage [We show that IHL was 28% lower after a two-week low- compared to a high-GI/SFA diet. This is in line with previous studies investigating the effects of either differences in dietary GI or differences in dietary fat saturation [We hypothesized that a lower glycemic response could underlie improvements in IHL. Indeed, we found a significant effect of diet (Glycemic variability, measured as the coefficient of variation (%CV), over four weekdays was significantly lower during the low-GI/SFA diet when compared to the high-GI/SFA diet. This finding is in line with previous studies showing that a higher-glycemic-index diet significantly increased glycemic variability [One of the principal pathways leading to increases in IHL is hepatic de novo lipogenesis [Another potential mechanism explaining the reduced IHL and lower glycemic response may involve changes in hepatic glycogen levels. Filled hepatic glycogen stores reduce the need for glucose entering the liver in the postprandial state to be used for glycogen storage, and as a result, glucose can be directed towards DNL [Similar to hepatic glycogen, no differences were found in whole-body substrate oxidation during the night after two weeks of a low- compared to a high-GI/SFA diet. As there were no pronounced differences in hepatic glycogen content on a low- compared to a high-GI/SFA diet, there was possibly no trigger to increase overnight fat oxidation in the low-GI/SFA diet. After a breakfast test meal in the low-GI/SFA diet, substrate oxidation seemed to shift from carbohydrate to fat oxidation in the first two hours postprandially. However, the differences did not reach statistical significance. As expected, total energy expenditure was also not significantly different after the two corresponding breakfast meals (Next to the possible pathways that could underlie the changes in IHL investigated here (DNL and fat oxidation), other pathways may also contribute to liver fat accumulation. For example, FFA uptake, dietary fat storage, and VLDL-TG secretion could be influenced by dietary GI/SFA content and should be considered in future studies. Luukkonen et al. showed that overfeeding saturated fatty acids increased adipose tissue lipolysis while overfeeding unsaturated fatty acids decreased it [To our knowledge, this is the first study examining the combined effect of reducing both GI and SFA content on IHL in a diet that can be achieved in real-life with habitual foods. Remarkably, IHL was already reduced after two weeks’ time. Moreover, the changes in IHL were not related to weight differences. The intervention diets did not differ in energy content and total fat and carbohydrates, which highlights the importance of macronutrient quality in the diet. Such dietary changes can be much more feasible for people at risk than implementing rigorous dietary plans aimed at weight loss. This reduction in IHL was accompanied by a lower glycemic response as measured by CGM during the standardized day 14 in the respiration chamber (