New research offers clues into how the body controls appetite and food intake

Concurrent with the national obesity epidemic has been a rise in the discoveries about how the body controls appetite and food intake.

In many of the new findings, research has identified a close relationship between the gastrointestinal endocrine system and the brain in regulating food intake. The relationship is expressed in coordination where circulating hormones convey information about food intake and appetite to brain pathways that control eating.

A team of researchers has added to this knowledge through their investigation of cholecystokinin (CCK) and glucagon-like-peptide-1 (GLP-1), two pre-absorptive signals that indicate when the appetite is satisfied (“satiety”). Both peptides are classical gastrointestinal hormones that are released into the circulation in response to meal consumption. Earlier research has documented that these peptides participate in controlling the appetite in healthy volunteers, and also in patients with obesity or Type II diabetes.

To further explore potential interactions between these two well-known satiety signals, the research team has examined the effects of CCK-33 and GLP-1 and the hormones’ interaction in the control of food intake and satiety in healthy subjects. The authors of the study, “Interaction between GLP-1 and CCK-33 in Inhibiting Food Intake and Appetite in Men,” are Jean-Pierre Gutzwiller, Lukas Degen, Daniel Matzinger, Sven Prestin, and Christoph Beglinger, all from the University Hospital, Basel, Switzerland. Their research appears in the Articles in PresS section of the American Journal of Physiology –Regulatory, Integrative and Comparative Physiology. The journal is one of 14 journals published monthly by the American Physiological Society (www.the-aps.org).

Twenty-four male volunteers completed the study (mean age 23 years, range 21-29 years, BMI 23.2±0.8). Inclusion criteria were BMI within 15% of normal; age 20 to 35; non-smoker; history of good health, no active medical problems, and under no medication; no history of food allergy or dietary restriction; and normal physical examination and laboratory screening results.

The study employed a randomized, placebo-controlled, double-blind, four-way crossover design in which each subject underwent four tests with the infusion of: saline, CCK-33, GLP-1, or CCK-33 plus GLP-1. Test trials were separated by at least seven days. GLP-1 and CCK-33 were intravenously infused alone or in combination into normal-weight men for 60 minutes before they were served a lunch of ham sandwiches, chocolate mousse and orange juice.

After the start of the perfusion, subjects scored their subjective feelings for hunger and fullness at 15-min intervals for the duration of each experiment using a visual analogue scale from 1 through 10 and indicated their scores on a questionnaire. A score of 0 for hunger indicated that the subject was not hungry at all, a score of 2 indicated "slightly hungry," 5 indicated "moderately hungry," 8 indicated "very hungry," and 10 indicated "absolutely ravenous." The score for fullness was similar.

The researchers found that physiological doses of CCK-33 and GLP-1 each reduced calorie consumption, but that simultaneous CCK-33/GLP-1 infusions produced infra-additive effects on meal size and calorie intake. In contrast, intravenous infusion of GLP-1 and CCK-33 had little effect on feelings of hunger, but simultaneous GLP-1/CCK-33 infusions produced a synergetic effect on hunger feelings in the pre-meal period. They also found that both GLP-1 and CCK-33 had small but non-significant effects on hunger feelings in the pre-meal period. A marked inhibition of hunger occurred, however, when these same GLP-1 and CCK-33 doses were infused together.

The mechanism(s) by which CCK and GLP-1 impact modulation of food intake in humans remains unclear. But this research demonstrates that CCK and GLP-1 are meal-related satiety signals that are released from the gastrointestinal tract during food intake. Both peptides promote a sense of fullness that encourages an end to the meal. Therefore, both peptides are factors that trigger the termination of eating, participating in a meal-to-meal control system. The researchers suggest that much more information is necessary to understand the basic physiological mechanisms that control food intake and satiety.