A Human Hormone, Combined With A Full Stomach, Offers Clues For
Understanding Our Food Intake

NOVEMBER 29, 2003 (Bethesda, MD) – With the holidays come the traditions of sharing meals, desserts and treats with family, friends and co-workers. But the need to reduce the amount of food we consume daily – during the holiday season and throughout the year --  has acquired a greater sense of urgency in the wake of America’s obesity epidemic. As scientists look for ways to help us battle the bulge, a new study suggests that our own hormonal makeup may offer promising clues. A team of researchers has tested the hypothesis that gastric distension in humans can enhance the effect of cholecystokin (CCK) on the reduction of food intake. The researchers conclude that CCK's suppression of food intake is enhanced when the stomach is distended.  

Background

CCK is a hormone released when digested fats and proteins are present, and reduces food intake. CCK stimulates enzyme secretion in the pancreas. The process eventually leads to inhibiting gastric emptying of the stomach’s foods, thereby causing gastric distension.  It has been suggested that increased gastric distension, induced by slowing of gastric emptying, may be the method by which CCK reduces food intake.

A New Study

The research team of Harry R. Kissileff, Julie C. Carretta, Allan Geliebter, and F. Xavier Pi-Sunyer, College of Physicians and Surgeons, Columbia University, New York, NY and the New York Obesity Research Center, St. Luke's/Roosevelt Hospital Center, New York, NY are the authors of a new study. Their investigation, entitled “Cholecystokinin and Stomach Distension Combine to Reduce Food Intake in Humans,” appears in the November 2003 edition of the American Journal of Physiology–Regulatory, Integrative and Comparative Physiology.  The journal is one of 14 scientific journals published each month by the American Physiological Society (APS).

Methodology

Researchers used the protocol outlined below:

Subjects: Eight nonobese males and eight nonobese female volunteers in good health participated in the study. All met the following criteria: weight within 15% of the desirable weight for height; between the ages of 18 and 35, nonsmokers with no active medical problems or taking any medications; had no allergies or history of weight problems; and were unrestrained eaters. Participants were also screened to eliminate candidates that did not like the test meal food.

Subjects received a written description of the study, indicating that the study’s purpose was to determine the effects of a balloon filled in their stomach to reactions on subsequent food consumption. They were advised that both a balloon and an intravenous catheter (IV) would be inserted every session, and that on different days either a protein or saline would be infused.

Procedures: Each subject reported to the laboratory six times after an overnight fast, given a standardized 300-kcal breakfast of one English muffin with butter and apple juice, which they consumed prior to leaving the lab. They were instructed not to eat or drink anything except water before returning to the laboratory 2.25 h later. When the subject returned, the back of his/her throat was anesthetized and a thin latex balloon (attached to a double-lumen tube) was passed orally into the stomach. A catheter connected to a dual-reservoir portable infusion pump was inserted into a vein, and saline was infused. Each of the two reservoir bags connected to the pump contained 40 ml of infusate. One reservoir always contained isotonic saline, and, depending on the peptide administration schedule, the other reservoir bag contained either CCK or saline as the test solution. The subject was given time to adjust to the infusion and balloon.  

When the subject felt comfortable, the balloon was filled with warm water. The tube was then gently retracted until resistance was met at the cardia and then pushed back down to prevent obstruction of the gastroesophageal junction. The end of the tube exiting the mouth was anchored, securing the balloon's position in the stomach. The tube was connected to a water manometer to record stomach pressure during and after balloon filling. Immediately after the balloon was positioned and secured, it was emptied.

Questionnaires: The subject was instructed to fill out the first questionnaire (baseline). After completing it, the balloon was filled to 100 ml at the rate of 100 ml/min. The subject was then instructed to fill out the second questionnaire.  After filling it out, the balloon was filled to 200 ml and the subject completed the third survey.  The balloon was then filled to 300 ml, and the subject filled out the fourth questionnaire. Then, infusion of either CCK-8 or saline began and continued for 21 min. Two minutes before the IV infusion terminated, subjects completed a fifth questionnaire before being served a yogurt shake and instructed to consume as much of it as they would during a normal meal. Five minutes after indicating they were finished, they filled out the sixth questionnaire. The balloon was then emptied and the  participant filled out the seventh questionnaire, after which the balloon was removed. After removal of the balloon and IV, the subject answered the postmeal questionnaire.

Analysis: For the last four test sessions subjects were assigned to one of four Latin square sequences of the peptide (CCK or saline) and distension (balloon filled or unfilled), and the four sequences counterbalanced.  Treatment was considered to be a single variable at four levels, two levels of distension (0 and 300 ml) crossed with two levels of infusion (CCK and saline). Ratings were analyzed using a  three-way mixed-model ANOVA. Planned comparisons among treatments were made for each sex, separately and for both sexes together. In all analyses of intake and duration, a probability of 0.05 was deemed statistically significant. The Bonferroni procedure was used for the questionnaires to adjust the significance level of the questionnaire data. 

Results

Highlights of the results included the following observations: 

•  The combination of CCK and distension of 300 ml reduced food intake by a mean of 200 g compared with the saline nondistension condition.

• CCK reduced intake significantly when the stomach was distended. Without distension, CCK did not significantly reduce intake in men but did significantly reduce intake in women.

• Distension alone had little effect. In contrast, during CCK infusion, intake was significantly lower after distension compared with nondistension in men but was not significantly lower in women. This is the one contrast in which men and women differed, although the difference between them was not significant.

• Because CCK combined with (but not without) distension significantly reduced intake, CCK enhanced the distension effect by an average (both sexes combined) of 73 g. Put another way, the CCK effect was 73 g greater with than without distension. However, this interaction effect was not significant in either sex alone or in the two sexes together.

• Meal duration was reduced significantly by CCK combined with 300 ml of distension in both sexes. CCK reduced meal duration significantly when the stomach was distended but the reduction was not significant in either sex alone, unlike intake. Distension alone reduced meal duration in men (unlike intake) but not in women and not in both sexes together (similar to intake).

Conclusions

The main results for the genders together showed a significant reduction in intake after a combination of CCK and distension, supporting the notion that gastric distension, rather than nutrient content, is likely to be the major determinant of the enhanced food intake-reducing effect of CCK. Taken together, all the findings suggest that the combination of a gastric distension with stimulation of CCK receptors could lead to the development of an effective appetite-suppressing agent that relies on natural satiety-inducing processes.

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Source: November 2003 edition of the American Journal of Physiology–Regulatory, Integrative and Comparative Physiology.  The journal is one of 14 scientific journals published each month by the American Physiological Society (APS).

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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Editor’s Note: A copy of the research article is available in pdf format to the press. Members of the press are invited to obtain a pdf copy of the study and to interview members of the research team. To do so, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.