Effects of orlistat on postprandial responses to meals high in protein and fiber

Adrienne M Hatch, Purdue University

Abstract

The prevalence of obesity has led to pharmaceutical developments of weight-loss drugs; currently one FDA approved weight-loss drug is on the market. Orlistat is a lipase inhibitor acting in the lumen of the small intestine to decrease fat absorption. Digestive products of dietary fat are stimulants of postprandial satiety hormones that signal feelings of fullness and serve as an indication to stop eating. Inhibiting fat absorption has the potential to attenuate the release of these postprandial signals, which may interfere with the effectiveness of the weight loss drug. Specifically, CCK is released in response to long chain fatty acids containing 10 or more carbons; therefore, the type of fat present is important. Although only a small amount of digested fat is required to elicit postprandial responses, literature has shown that orlistat has had an effect. Meals containing high amounts of protein and fiber have been shown to increase the postprandial gut hormone and satiety responses that orlistat may attenuate. While many studies have examined effects of the prescription form of orlistat (120 mg), there has not been much research done on the over-the-counter form (alli®, 60 mg). The purpose of this study was to examine the effects of alli® in combination with meals that are higher in protein and fiber on postprandial cholecystokinin (CCK), ghrelin, glucose, insulin, metabolic and appetitive responses. Exploratory analyses were done to examine the effects of alli® on palatability ratings and desire to eat fat. Results showed a significant effect of meal and drug on the postprandial glucose response in that the HPF meal resulted in a lower mean postprandial glucose response compared to the NPF meal, and alli® led to a higher glucose response compared to the placebo. Insulin showed a lower postprandial response to the HPF meal compared to the NPF meal. A significant meal-by-drug interaction effect on the postprandial CCK response showed that CCK was lower with alli® compared to the placebo with NPF meals, but not HPF meals. There were no significant main effects or meal-by-drug interaction effects on the postprandial ghrelin response. The HPF meal significantly lowered the respiratory quotient compared to the NPF meal and resulted in borderline significance for increasing the metabolic rate compared to the NPF meal. There were no significant main effects or meal-by-drug interaction effects on postprandial appetitive responses, except for desire to eat. Compared to the NPF meal, the HPF meal resulted in a greater decrease in desire to eat with the placebo treatment, but not with the alli® treatment. Postprandial fullness had a borderline significant main effect of meal, in which the HPF meal elicited a greater fullness response. Palatability ratings of the test breakfast were not significantly related to glycemic and insulinemic responses, or metabolism. No significant effects occurred for desire to eat fat. A borderline significant interaction effect on lunch intake showed lower caloric consumption during alli® use on the HPF diet. The results of this study suggest a potential benefit to consuming meals higher in protein and fiber while alli® is taken. Not only may they raise the CCK response (potentially affecting appetite, gastric emptying, gallbladder contraction, and pancreatic secretion), but also lower the glucose and insulin responses that can reduce the desire to eat. Consuming HPF meals were shown to increase metabolic rate and fat oxidation, independent of alli ® use. A borderline significant effect of the HPF meal on satiety occurred, indicating a need for further research. Future studies should examine the longterm effects of orlistat use during periods of energy restriction in combination with high protein and fiber diets, as well as distinguish between the separate and combined effects of protein and fiber on postprandial responses during orlistat use. Further research is needed to determine the implications of our results during periods of weight loss when fat and energy restriction take place. (Abstract shortened by UMI.)

Degree

M.S.

Advisors

McCrory, Purdue University.

Subject Area

Nutrition

COinS