Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2003
Publication Date: 1/1/2004
Citation: Teff, K.T., Elliott, S.S., Tschoep, M., Rader, D., Heiman, M., Townsend, R.R., Keim, N.L., D'Alessio, D., Havel, P.J. 2004. Consuming high-fructose beverages with meals reduces circulating insulin and leptin concentrations and raises plasma ghrelin and triglycerides in normal weight women. Clinical Endocrine Metabolism. 89(6):2963-2972, 2004. Interpretive Summary: Several new hormones, including leptin and ghrelin, have been discovered that are thought to be involved in the regulation of food intake and body weight in humans. Studies conducted with animals suggest that the metabolism of the sugar, glucose, may trigger the release of leptin and suppress the release of ghrelin. We conducted a study to compare the effects of consuming two different sugars commonly found in sweetened beverages, glucose and fructose, on the amounts of these hormones circulating in the blood. Compared to consumption of glucose, consumption of fructose was associated with lower circulating levels of blood glucose, insulin, and leptin and higher circulating levels of ghrelin and triglycerides. Therefore, the consumption of large quantities of fructose-sweetened beverages could lead to increased hunger and food intake, and, over longer periods of time, could lead to weight gain.
Technical Abstract: Previous studies suggest that leptin secretion is regulated by insulin-mediated glucose metabolism. Since fructose, unlike glucose, does not stimulate insulin secretion, we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose. Blood samples were collected every 30-60 minutes for 24 hours from 12 normal-weight women on 2 randomized days during which the subjects consumed 3 meals containing 55/30/15% of total kilocalories (kcal) as carbohydrate, fat, and protein, respectively with 30% kcal as either a fructose-sweetened (HFr) or glucose-sweetened (HGl) beverage. Post-prandial glycemic excursions were reduced by 66 ± 12% and insulin responses were 65 ± 5% lower (both p< 0.001) during HFr consumption. The area under the curve (AUC) for leptin during the first 12 h and the entire 24 h were 33±7% (p< 0.005) and 21 ± 8% (p< 0.02) smaller, respectively, on the HFr day compared to the HGl day. Plasma ghrelin levels were suppressed by ~30% 1-2 hours following ingestion of each HGl meal (p< 0.01), but not after HFr meals (p< 0.05 vs HGl). Consumption of high fructose meals produced a rapid and day long elevation of plasma triglycerides that was not observed on the HGl day. Since insulin and leptin function as signals to the CNS in the long-term regulation of energy balance, decreases of circulating insulin and leptin and increased ghrelin concentrations as demonstrated in this study could lead to decreased satiety, increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of high fructose diets.