Metabolic effects of the dietary monosaccharides fructose, fructose–glucose, or glucose in mice fed a starch‐containing moderate high–fat diet

Abstract

Fructose consumption has been linked to obesity and increased hepatic de novo lipogenesis (DNL). Excessive caloric intake often confounds the results of fructose studies, and experimental diets are generally low‐fat diets, not representative for westernized diets. Here, we compared the effects of dietary fructose with those of dietary glucose, in adult male and female mice on a starch‐containing moderate high–fat (HF) diet. After 5 weeks fattening on a HF high‐glucose (HF‐G) diet, mice were stratified per sex and assigned to one of the three intervention diets for 6 weeks: HF high fructose (HF‐F), HF with equimolar glucose and fructose (HF‐GF), or HF‐G. Bodyweight (BW) and food intake were measured weekly. Indirect calorimetry was performed on week 5; animals were sacrificed in food‐deprived state on week 6. Data were analyzed within sex. BW gain was similar among animals on the HF‐G, HF‐GF, and HF‐F diets. Cumulative food intake was slightly lower in HF‐F animals (both sexes). However, energy expenditure was not affected, or were circulating insulin and glucose concentrations, and hepatic triglyceride levels at endpoint. Hepatic gene expression analysis showed only minor alterations in hexokinase and glycolysis‐related expression in males, and no alterations in sugar transporters, or DNL‐related enzymes. In females, no consistent alterations in hepatic or small intestine gene expression were seen. Concluding, partial or complete replacement of dietary glucose with fructose does not increase caloric intake, and does not affect BW, hepatic triglyceride levels, or insulin concentrations in male and female mice on a moderate high–fat diet.

Adaptation of fuel selection to acute decrease in voluntary energy expenditure is governed by dietary macronutrient composition in mice

“…Yet, the wheel‐omission‐mediated fuel oxidation changes are beyond merely reflecting the diet, since both diets, though to different proportions, include both carbohydrates and fat, and it is the wheel omission that decreased fuel oxidation specifically of the minor nutritional source, which had been utilized under conditions of greater energy demand. In support of the effect of dietary composition on fuel selection for oxidation, a recent report demonstrated that supplementing moderately HFD with monosaccharides (fructose and glucose), resulted in higher mean RER during the active phase (Bouwman et al, 2020 ).…”

Effect of lifelong sucrose consumption at human-relevant levels on food intake and body composition of C57BL/6N mice

“…Our results seem to be similar to that of Ruff et al ( 17 ), who reported that a 25% kcal sugar (as 1:1 fructose:glucose) diet for >26 weeks did not affect body weight. The study by Bouwman et al ( 21 ) also showed that partial or complete replacement of glucose with fructose did not lead to overeating and weight gain in mice on a moderately high-fat diet, and high fructose intake at up to 30% daily kcal did not lead to overeating and weight gain in healthy subjects compared to controls with NAFLD ( 23 ). However, since body weight is not an accurate indicator of obesity, we also assessed the body composition of the mice regularly, and overall found no significant differences between groups over the whole life span of the mice.…”

“…The fructose moiety of sucrose and HFCS has been suggested to be the culprit of potential detrimental health effects associated with high sugar intake ( 14 , 15 ), such as insulin resistance, glucose intolerance, hyperglycemia, and hypertriglyceridemia in animals in the short-term ( 16 , 17 ), as well as reduced lifespan and fecundity ( 17 – 20 ). However, some researchers have suggested that high fructose/sugar intake may not cause overeating, obesity, hepatic lipid accumulation, dyslipidemia, and hyperinsulinemia ( 21 – 23 ).…”

Novel insights in intestinal and hepatic fructose metabolism: from mice to men

“…Although previous animal studies have shown that fructose favours hepatic de novo lipogenesis more than glucose [21], Bouwman et al [22] recently failed to replicate these findings. They did not observe a difference in hepatic triglyceride accumulation nor in the expression of lipogenic genes in mice fed either glucose or fructose.…”