Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.

The presence of nutrients in the small intestine slows gastric emptying and suppresses appetite and food intake; these effects are partly mediated by the release of gut hormones, including CCK. We investigated the hypothesis that the modulation of antropyloroduodenal motility, suppression of appetite, and stimulation of CCK and glucagon-like peptide-1 secretion by intraduodenal fat are dependent on triglyceride hydrolysis by lipase. Sixteen healthy, young, lean men were studied twice in double-blind, randomized, crossover fashion. Ratings for appetite-related sensations, antropyloroduodenal motility, and plasma CCK and glucagon-like peptide-1 concentrations were measured during a 120-min duodenal infusion of a triglyceride emulsion (2.8 kcal/min) on one day with, on the other day without, 120 mg tetrahydrolipstatin, a potent lipase inhibitor. Immediately after the duodenal fat infusion, food intake at a buffet lunch was quantified. Lipase inhibition with tetrahydrolipstatin was associated with reductions in tonic and phasic pyloric pressures, increased numbers of isolated antral and duodenal pressure waves, and stimulation of antropyloroduodenal pressure-wave sequences (all P < 0.05). Scores for prospective consumption and food intake at lunch were greater, and nausea scores were slightly less, and the rises in plasma CCK and glucagon-like peptide-1 were abolished (all P < 0.05). In conclusion, lipase inhibition attenuates the effects of duodenal fat on antropyloroduodenal motility, appetite, and CCK and glucagon-like peptide-1 secretion.

Plasma glucagon-like peptide-1 (GLP-1) responses to duodenal fat and glucose infusions in lean and obese men.

It has been suggested that obesity is associated with a reduced glucagon-like peptide-1 (GLP-1) response to oral carbohydrate, but not fat. The latter may, however, be attributable to changes in gastric emptying. We have assessed plasma GLP-1 levels in response to these infusions in lean and obese subjects. Seven healthy lean (body mass index (BMI), 19.1-24.6 kg/m(2)) and seven obese (BMI, 31.3-40.8 kg/m(2)) young men received an intraduodenal infusion of glucose and fat for 120 min (2.86 kcal/min) on two separate days. Blood samples for plasma GLP-1 were obtained at baseline and every 20 min during the infusion. Plasma GLP-1 increased during infusion of glucose and fat (P = 0.001), but there were no differences between lean and obese subjects, nor the two nutrients. We conclude that GLP-1 secretion in response to duodenal infusion of glucose and fat is not altered in obese subjects.

Carbohydrate and satiety.

This review focuses on what is known about the effects of carbohydrate on food intake, the potential mechanisms mediating these effects, and the impact of different monosaccharides in humans. The inhibition of subsequent food intake associated with ingestion of carbohydrate appears to result primarily from gastrointestinal signals, including those generated by orosensory stimulation, gastric distension, and perhaps most importantly the interaction of nutrients with receptors in the small intestine. The latter is associated with the release of putative satiety hormones, including glucagon-like peptide-1 and amylin, and slowing of both gastric emptying and small intestinal transit (thereby prolonging gastric distension and increasing the time available for nutrient absorption). The effects of carbohydrate on food intake are dependent on the route of administration (i.e., oral, intragastric, or intraduodenal). Changes in blood glucose and insulin concentrations per se probably do not play a major role in the induction of satiety. Studies relating to the comparative effects of different monosaccharides/carbohydrates have yielded inconclusive results, probably in part owing to substantial differences in methodological approaches.

Postprandial hypotension in response to duodenal glucose delivery in healthy older subjects.

Postprandial hypotension occurs frequently in older people and may lead to syncope and falls. Some recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate of gastric emptying. The aim of this study was, therefore, to determine whether the fall in blood pressure induced by intraduodenal glucose is influenced by the rate of nutrient delivery into the small intestine, bypassing the effects of gastric emptying. Eight healthy elderly subjects (four male and four female, age 70.3 +/- 3.4 years) were studied on two separate days, in double-blind, randomised order. Glucose was infused intraduodenally at a rate of either 1 or 3 kcal min(-1), for 60 min, (0-60 min) followed by 0.9 % saline for a further 60 min (60-120 min). Blood pressure and heart rate were recorded at baseline and every 3 min during the study. Blood glucose and plasma insulin were also determined. Only the 3 kcal min(-1) infusion caused a significant fall in systolic (P < 0.001) and diastolic (P < 0.0001) blood pressure and an increase in the heart rate (P < 0.0001). The rises in blood glucose (P < 0.01) and plasma insulin (P < 0.05) concentrations were greater during the 3 kcal min(-1) infusion. We conclude that in healthy older subjects, the magnitude of the fall in blood pressure and increase in heart rate induced by intraduodenal glucose infusion is dependent on the rate of nutrient delivery into the small intestine. These results may have relevance to the treatment of postprandial hypotension.