The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19–47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions (P < 0.001) and energy intake (control: 4,604 ± 464 kJ, C10: 4,109 ± 588 kJ, and C12: 1,747 ± 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea (P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control (P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs (P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs (P = 0.004). C12 and C10 increased plasma CCK (P < 0.001), but the effect of C12 was substantially greater (P = 0.001); C12 stimulated GLP-1 (P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.

It is not well recognized that in the elderly weight loss is more common than weight gain. The aim of this analysis was to determine the effect of ageing on appetite (hunger/fullness) and energy intake, after overnight fasting and in a postprandial state, by meta-analyses of trials that included at least two age groups (>18 years). We hypothesized that appetite and energy intake would be less in healthy older compared with younger adults. Following a PubMed-database systematic search up to 30 June 2015, 59 studies were included in the random-effects-model meta-analyses. Energy intake was 16%–20% lower in older (n = 3574/~70 years/~71 kg/~25 kg/m²) than younger (n = 4111/~26 years/~69 kg/~23 kg/m²) adults (standardized mean difference: −0.77 (95% confidence interval −0.90 to −0.64)). Hunger was 25% (after overnight fasting; weighted mean difference (WMD): −17 (−22 to −13) mm) to 39% (in a postprandial state; WMD: −14 (−19 to −9) mm) lower, and fullness 37% (after overnight fasting; WMD: 6 mm (95% CI: 1 to 11 mm)) greater in older than younger adults. In conclusion, appetite and energy intake are less in healthy older than younger adults, suggesting that ageing per se affects food intake.

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals ( P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals ( P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

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.

The presence of fat in the small intestine slows gastric emptying, stimulates the release of many gastrointestinal hormones, and suppresses appetite and energy intake as a result of the digestion of fats into free fatty acids; the effects of free fatty acids are, in turn, dependent on their chain length. Given these effects of fat, it is paradoxical that high dietary fat intakes have been linked to increased energy intake and body weight and are considered to play a significant role in the pathogenesis of obesity. However, increasing evidence indicates that a chronic increase in dietary fat is associated with an attenuation of the feedback signals arising from the small intestine induced by fat, with a consequent relative acceleration of gastric emptying, modulation of gastrointestinal hormone secretion, and attenuation of the suppression of energy intake. This review addresses the gastrointestinal factors involved in the regulation of appetite and energy intake, with a particular focus on 1) the gastrointestinal mechanisms triggered by small intestinal fat that modulate energy intake, 2) the potential role of a high dietary fat intake in the development of obesity, and 3) implications for the prevention and management of obesity.