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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CCK-AR–/– mice have normal pancreatic histology and blood glucose levels...
CCK-AR–/– mice have normal pancreatic histology and blood glucose levels (a) Normal histology of exocrine and endocrine pancreatic tissue from CCK-AR–/– mice. Non-β islet cells were immunostained; sections were counterstained with hematoxylin and eosin. Both the islet and acinar gland morphology are comparable in wild-type (WT) and CCK-AR–/– (knockout, or KO) mice (see text). The pancreatic histology that is shown is representative of sections from five age-matched pairs (WT and CCK-AR–/–) of male mice. (b) Blood glucose levels in CCK-AR–/– mice are not significantly different from the respective values of age- and sex-matched wild-type controls. Morning glucose levels were determined in freely fed mice. Average age and number of animals in the corresponding groups were as follows: 311 ± 53 days (12 wild-type males); 286 ± 57 days (10 CCK-AR–/– males); 307 ± 54 days (15 wild-type females); 330 ± 54 days (14 CCK-AR–/– females). Data are given as mean ± SD. Student's t values for glucose comparisons between wild-type and CCK-AR–/– mice were: t(20) = 0.27, P = 0.79 (males); t(27) = 1.46, P = 0.16 (females).