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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 6 2963-2972
Copyright © 2004 by The Endocrine Society

Dietary Fructose Reduces Circulating Insulin and Leptin, Attenuates Postprandial Suppression of Ghrelin, and Increases Triglycerides in Women

Karen L. Teff, Sharon S. Elliott, Matthias Tschöp, Timothy J. Kieffer, Daniel Rader, Mark Heiman, Raymond R. Townsend, Nancy L. Keim, David D’Alessio and Peter J. Havel

Monell Chemical Senses Center (K.L.T.) and Department of Medicine (K.L.T., D.R., R.R.T.), University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Nutrition, University of California, Davis (S.S.E., P.J.H.), Davis, California 95616; University of British Columbia (T.J.K.), Vancouver, British Columbia, Canada V6T 1Z4; Eli Lilly (M.T., M.H.), Indianapolis, Indiana 46285; U.S. Department of Agriculture, Western Human Nutrition Research Center (N.L.K.), Davis, California 95616; and Department of Medicine, University of Cincinnati (D.D.), Cincinnati, Ohio 45267

Address all correspondence and requests for reprints to: Peter J. Havel, D.V.M., Ph.D., Department of Nutrition, University of California, Davis, One Shields Avenue, Davis, California 95616. E-mail: pjhavel{at}ucdavis.edu.

Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism. Because 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 min for 24 h from 12 normal-weight women on 2 randomized days during which the subjects consumed three meals containing 55, 30, and 15% of total kilocalories as carbohydrate, fat, and protein, respectively, with 30% of kilocalories as either a fructose-sweetened [high fructose (HFr)] or glucose-sweetened [high glucose (HGl)] beverage. Meals were isocaloric in the two treatments. Postprandial 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 for leptin during the first 12 h (–33 ± 7%; P < 0.005), the entire 24 h (–21 ± 8%; P < 0.02), and the diurnal amplitude (peak – nadir) (24 ± 6%; P < 0.0025) were reduced on the HFr day compared with the HGl day. In addition, circulating levels of the orexigenic gastroenteric hormone, ghrelin, were suppressed by approximately 30% 1–2 h after ingestion of each HGl meal (P < 0.01), but postprandial suppression of ghrelin was significantly less pronounced after HFr meals (P < 0.05 vs. HGl). Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day (P < 0.005). Because insulin and leptin, and possibly ghrelin, function as key signals to the central nervous system 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 increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose.

This work was supported by a grant from the Human Nutrition Institute of the International Life Sciences Institute Research Foundation (ILSI RF); National Institutes of Health Grants DK-35747, DK-58108, and M01-RR00042; the American Diabetes Association; The American Physiological Society; and the U.S. Department of Agriculture.

The opinions expressed herein are those of the authors and do not necessarily represent the views of ILSI RF.

Abbreviations: AUC, Area under the curve; CNS, central nervous system; FFA, free fatty acid; GCRC, General Clinical Research Center; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; HFCS, HFr corn syrup; HFr, high fructose; HGl, high glucose; TG, triglyceride.




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