Food for thought: a critique on the hypothesis that endogenous cholecystokinin acts as a physiological satiety factor

This review evaluates the various lines of evidence supporting the hypothesis that cholecystokinin (CCK) released from the small intestine during feeding plays a physiological satiety. Issues considered include, the effects of systemic injection of CCK on consummatory and operant feeding, the role of the vagus nerve, the effects of CCKB receptor antagonists, and the neuroendocrine responses to exogenous CCK. A critical appraisal of this research indicates that while it is clearly demonstratable that exogenous peripheral CCK can alter food intake by acting on CCKA receptors, the mechanism involved may be more closely related to the induction if aversion and nausea, rather than satiety. With regard to peripheral endogenous CCK, the available evidence also does not seem to support a role for the hormone in satiety. In particular, it is doubtful whether plasma concentrations of CCK following a meal are sufficiently high to inhibit feeding. Moreover, CCKA receptor antagonist which do not cross the blood brain barrier fail to increase meal size, as would be expected if peripheral CCK was an effective satiety factor. In addition, the recent literature concerned with the possibility that CCK may have a direct action within the brain in the control of food intake has been reviewed. These studies show that CCK administered intracerebroventicularly, or by micoinjection into discrete brain regions, also inhibits feeding via a CCKA receptor mechanism. However, the physiological relevance of these findings have yet to be determined.