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Effect of Exogenous Cholecystokinin (CCK)-8 on Food Intake and Plasma CCK, Leptin, and Insulin Concentrations in Older and Young Adults: Evidence for Increased CCK Activity as a Cause of the Anorexia of Aging

Department of Medicine (C.G.M., J.W., M.H., I.M.C.), University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia 5000; Division of Clinical Biochemistry (H.M.), Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia; Department of Gastroenterology and Hepatology (J.B.M.J.J.), Radboud Ziekenhuis, 6525ED Nijmegen, The Netherlands; 6525ED and St. Louis University Health Sciences Center (J.E.M.), Division of Geriatric Medicine and Geriatric Research Education and Clinical Center, St. Louis, Missouri 63104

Address all correspondence and requests for reprints to: Dr. Ian Chapman, Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, Australia 5000. E-mail: ian.chapman{at}adelaide

Abstract

Healthy aging is associated with reductions in appetite and food intake—the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on the satiating effects of CCK, 12 young and 12 older healthy subjects received 25-min iv infusions of saline (control) and CCK-8, 1 ng/kg per min or 3 ng/k per min, on 3 separate days before a test meal. Older subjects ate less than young subjects, and food intake was suppressed 21.6% by CCK-8, compared with the control day (P < 0.05). The suppression of energy intake by CCK-8 in older subjects was twice that in young subjects (32 ± 6% vs. 16 ± 6% SEM, P < 0.05) and was related to plasma CCK-8 concentrations, which were higher at baseline (P < 0.05) and increased more during CCK-8 infusions in older than young subjects (P < 0.01). The extent of suppression of food intake per given rise in plasma CCK-8 concentrations did not differ between the two age groups (P = 0.35). Endogenous CCK concentrations were higher at baseline in older subjects (P < 0.001) and decreased during the CCK-8 but not control infusions (P < 0.01), suggesting that CCK suppresses its own release. Plasma leptin concentrations were not affected by CCK infusion, whereas postprandial insulin concentrations were lowered and the peak postprandial glucose concentration was delayed but not affected by CCK-8 infusion. Because older people retain their sensitivity to the satiating effects of exogenous CCK and plasma endogenous CCK concentrations are higher in older people, increased CCK activity may contribute to the anorexia of aging.

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