Determinants of fructose metabolism after consumption of a sugar‐rich liquid meal in healthy humans
Authors: Urowska Anna , De Giorgi Sara , Hodson Leanne , Laville Martine , Tappy Luc 
Published: November 2023

The fructose component of dietary sugars is mainly converted into lactate, glucose and fatty acids in splanchnic organs. The mechanism regulating the partitioning of fructose carbons into each of these pathways is largely unknown. We therefore measured the metabolic fate of fructose ingested in a liquid mixed meal, in sixteen healthy volunteers (7 males and 9 females) and assessed how fructose partitioning was related to body mass index (BMI) or insulin sensitivity parameters in healthy individuals with a BMI between 19.5 kg/m2 and 42.3 kg/m2 and aged 22 – 47 years.All participants consumed a weight‐maintenance diet containing 20% sucrose for 3 days. Thereafter, on the fourth day, they were studied during the fasting state and in the postprandial state for 6 hours after ingestion of a mixed liquid meal containing 7.80 ± 0.01 kcal, 0.3 g lipid, 0.3 g protein, 0.5 g glucose and 0.5 g fructose labelled with 1% 13C6‐fructose per kg total body weight. Plasma concentration and 13C‐isotopic enrichments of glucose, lactate and of palmitic acid associated with triglyceride‐rich lipoproteins (TRL‐13C‐palm), whole body glucose rate of appearance (measured with 6,6‐deuterated glucose) and whole body 13CO2 production were measured over the course of the postprandial period.Postprandial fructosemia (area under the curve (AUC) were between 25.6–46.5 mmol/L*360min) and 13C‐lactate concentrations (AUC: 0.45–0.80 mmol/L*360min) were similar in each participant, suggesting that splanchnic fructose extraction and disposal of fructose carbons as lactate were relatively the same in each subject. Total fructose oxidation (9.9 – 16.4 g/6 hours) also showed little inter‐individual variations. In contrast TRL‐13C‐palm (AUC: 1.9 – 35.7 μmol/L*360min) and 13C‐glucose appearance in blood (AUC: 3.0 – 15.8 g/6 hours) were highly variable and were both positively correlated with body weight (r = 0.5, p<0.001 and r = 0.8, p<0.001 respectively) and with postprandial insulin AUCs (r = 0.5, p<0.001 and r = 0.5, p<0,001 respectively). This suggests that gluconeogenesis and de novo lipogenesis is enhanced in overweight or insulin‐resistant subjects. However, administration of meals with a calorie] content proportional to body weight resulted in individual fructose intakes ranging from 28.6 to 64.5 g. Normalization of data for total fructose intake, decreased the inter‐individual variability for 13C‐glucose appearance (0.10 – 0.35 g/g fructose ingested) and TRL‐13C‐palm AUC (0.06 – 0.45 μmol*360min/g), and correlations with insulin concentration or BMI no longer observed. In contrast, fructose oxidation and 13C‐lactate AUC normalized for fructose ingestion were negatively correlated with BMI and insulin.In summary, our data indicate that 1) administration of fructose proportional to body weight leads to fructose “overfeeding” in overweight vs normal weight subjects, 2) fructose carbon disposal as plasma glucose or TRL‐13C palmitate increases with increasing doses, while fructose disposal as lactate and total fructose carbon oxidation does not. This suggests that ingested fructose is metabolized preferentially as lactate, and that gluconeogenesis and lipogenesis are activated when the capacity to dispose of fructose as lactate is saturated.Support or Funding InformationSupported By the Swiss National Fund for Science