The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight
Alan S. Kopin, … , Robin Kanarek, Martin Beinborn
Alan S. Kopin, … , Robin Kanarek, Martin Beinborn
Published February 1, 1999
Citation Information: J Clin Invest. 1999;103(3):383-391. https://doi.org/10.1172/JCI4901.
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Article

The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight

Abstract

Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor–/– mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor–/– mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor–/– mice maintained normal body weight well into adult life. In addition, each of the two receptor–/– strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long-term maintenance of body weight.

Authors

Alan S. Kopin, Wendy Foulds Mathes, Edward W. McBride, Minh Nguyen, Wisam Al-Haider, Frank Schmitz, Susan Bonner-Weir, Robin Kanarek, Martin Beinborn

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Food and water intake is normal in freely fed CCK-AR–/– mice (a) Twenty-...
Food and water intake is normal in freely fed CCK-AR–/– mice (a) Twenty-four hour intake of water and Purina rodent laboratory chow are not significantly different (P > 0.05) between wild-type and CCK-AR–/– mice that were fed ad libitum. Average daily intake (mean ± SEM) over a 19-day period is shown. This study included 18 wild-type (WT) and 16 CCK-AR–/– mice. Student's t values for comparison between wild-type and CCK-AR–/– mice were: t(14) = 0.69, P = 0.50 (males, water); t(14) = 0.59, P = 0.57 (males, chow); t(16) = –1.02, P = 0.32 (females, water); and t(16) = 1.95, P = 0.07 (females, chow). (b) Normal diurnal variation in food intake of CCK-AR–/– mice. Eight wild-type and seven CCK-AR–/– mice were allowed ad libitum access to Purina rodent laboratory chow. Average intake of chow (mean ± SEM) during the light and dark cycles, each 12 h long, was recorded over a 14-day period. There was no significant difference (P > 0.05) between the intake of wild-type (WT) and CCK-AR–/– mice during either the light or the dark period. Student t values for comparison between wild-type and CCK-AR–/– mice were: t(13) = –0.74, P = 0.48 (food intake, dark); t(13) = 1.57, P = 0.14 (food intake, light).