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Human Plasma Ghrelin Levels Increase during a One-Year Exercise Program

Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington School of Medicine, and Veterans Affairs Puget Sound Health Care System (K.E.F.-S., R.S.F., D.E.C.), Seattle, Washington 98195; Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program (A.M., K.B.R., Y.Y., S.S.T.), Seattle, Washington 98109-1024; Department of Epidemiology, University of Washington School of Public Health and Community Medicine (A.M., K.B.R., S.S.T.), Seattle, Washington 98195; Department of Medicine, University of Colorado Health Sciences Center, School of Medicine (R.S.S.), Denver, Colorado 80262; and Department of Biostatistics, University of Washington (Y.Y.), Seattle, Washington 98195

Address all correspondence and requests for reprints to: Dr. David E. Cummings, University of Washington, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, S-111-Endo, Seattle, Washington 98108. E-mail: davidec{at}u.washington.edu.

Weight loss resulting from decreased caloric intake raises levels of the orexigenic hormone, ghrelin. Because ingested nutrients suppress ghrelin, increased ghrelin levels in hypophagic weight loss may result from decreased inhibitory input by ingested food, rather than from lost weight. We assessed whether ghrelin levels increase in response to exercise-induced weight loss without decreased caloric intake. We randomized 173 sedentary, overweight, postmenopausal women to an aerobic exercise intervention or stretching control group. At baseline, 3 months, and 12 months, we measured body weight and composition, food intake, cardiopulmonary fitness (maximal oxygen consumption), leptin, insulin, and ghrelin. Complete data were available for 168 women (97%) at 12 months. Exercisers lost 1.4 ± 0.4 kg (P < 0.05 compared with baseline; P = 0.01 compared with stretchers) and manifested a significant, progressive increase in ghrelin levels, whereas neither measure changed among stretchers. Ghrelin increased 18% in exercisers who lost more than 3 kg (P < 0.001). There was no change in caloric intake in either group and no effect on ghrelin of exercise per se independent of its impact on body weight. In summary, ghrelin levels increase with weight loss achieved without reduced food intake, consistent with a role for ghrelin in the adaptive response constraining weight loss and, thus, in long-term body weight regulation.

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