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J Clin Invest. 1999 Feb;103(3):383-91.

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

Author information

1
Department of Medicine, GRASP Digestive Disease Center, Tupper Research Institute, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. alan.kopin@es.nemc.org

Erratum in

  • J Clin Invest 1999 Mar;103(5):759.

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.

PMID:
9927499
PMCID:
PMC407901
DOI:
10.1172/JCI4901
[Indexed for MEDLINE]
Free PMC Article

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