Role of cholecystokinin and opioid peptides in control of food intake

Of the many factors that influence food intake, there is strong evidence that opioid and CCK peptides, which stimulate feeding and elicit satiety, respectively, are important components that may act in concert to regulate energy balance. Cholecystokinin peptides have been isolated in both the brain and gastrointestinal tract, and changes in concentration in the brain and in plasma have been shown to vary with feeding. Peripherally injected CCK has been shown to elicit satiety in many species, including humans, an effect that may be mediated in the CNS via the vagus. In several species, most notably the sheep, direct injection into the CSF potently decreases food intake. Questions remaining regarding the role of CCK peptides in eliciting satiety include the sites and mechanisms of action. It is unknown whether CCK acts directly on receptors, indirectly on some other parameter, or as a neurotransmitter. Although opioid peptides have also been localized in portions of both the periphery and brain, a specific physiological role for their presence has not yet been determined. Opioid peptides from three families--endorphins, enkephalins, and dynorphins--have been shown to stimulate feeding in various species. They have been active at several opioid receptor types in the CNS, but there is limited evidence to suggest they affect food intake when administered peripherally. In contrast, peripheral injection of opiate antagonists has effectively decreased food intake, an observation that led to the original hypothesis that opioids were involved in the hunger component in the control of food intake and that excess concentrations might be involved in the development of obesity. An increasing body of evidence supports the concept that opioid and CCK peptides may interact to control food intake, but the evidence is more suggestive than conclusive.