The Effect of Macronutrients on Satiety and Gut Hormone Responses

A Physiological Study on the Effect of Macronutrients Delivery to the Proximal and Distal Small Bowel on Satiety and Gut Hormone Responses

This study is part of a research theme aiming at elucidating the physiological mechanisms of action of weight loss after gastric bypass surgery. The Roux-en-Y Gastric Bypass procedure induces pronounced and sustained weight loss, but the physiological mechanisms of action are not completely clear. Neither mechanical restriction of food intake nor malabsorption, are the main contributing factors. The enhanced postprandial responses of gut hormones (e.g. GLP-1 and PYY) which increase satiety as well as energy expenditure after surgery suggest a changed physiological set point for appetite and metabolism.

Our hypothesis is that the intake of high quantity of protein in a microcapsule form would be able to reach the distal parts of the intestinal mucosa and stimulate maximum stimulation of the anorectic gut hormones. The higher functions of the brain will respond to these strong neuroendocrine signals by ensuing satiety and fullness.

Ten healthy volunteers, aged 18 to 65 years will be recruited. Each subject will be studied on six occasions one week apart. On each visit, a baseline serum sample will be drawn from each subject. In a randomized way all subjects will receive the following meals in their successive weekly visits: Option 1 High protein mixed meal in capsules that break down in the stomach, Option 2 High protein mixed meal in capsules that break down in the distal small bowel, Option 3 High fat mixed meal in capsules that break down in the stomach, Option 4 High fat mixed meal in capsules that break down in the distal small bowel, Option 5 High CHD mixed meal in capsules that break down in the stomach, Option 6 High CHD mixed meal in capsules that break down in the distal small bowel. On the same day, all subjects will be offered standard ad libitum meal to measure their food consumption. After 3 hours (i.e. at 12:00) another blood sample will be drawn. All subjects will be asked to rate their appetite on a Visual Analogue Scale (VAS). Upon VAS completion the subjects will be allowed to go home.

Inclusion Criteria:

• 18-65 years
• Normal fasting glucose
• Stable body weight for at least last three months
• BMI < 30 Kg/m2
• Capacity to consent to participate
• Independently mobile

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded:
• Pre-diabetes Diabetes
• Obesity
• Smoking
• Substance abuse
• Pregnancy
• Use of medications (except for oral contraceptives)
• Chronic medical or psychiatric illness
• Any significant abnormalities detected on physical examination, electrocardiography, or screening blood tests (measurement of complete blood count, electrolytes, fasting glucose, and liver function)