Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release

Hildebrand, Pius; Petrig, Christophe; Burckhardt, Beat; Ketterer, Sylvia; Lengsfeld, Hans; Fleury, André; Hadváry, Paul; Beglinger, Christoph

doi:10.1016/s0016-5085(98)70640-7

Cited by 81 publications

(79 citation statements)

References 24 publications

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“…Previous studies have only examined the effects of intragastric or intraduodenal administration of a lipase inhibitor (Orlistat), and have found that when administered with 30-55 g of stable triglyceride emulsions, CCK release is inhibited. [9][10][11][12] Hildebrand et al 9 demonstrated that intraduodenal perfusion of a 30 g olive oil solution resulted in a threefold increase in plasma CCK concentrations from basal levels during the first postprandial hour that remained elevated for the remaining 4 h. In contrast, plasma CCK concentrations did not increase significantly during the experiment when Orlistat was administered. 9 Thus adequate digestion of dietary triglycerides by pancreatic lipase to produce FFAs is necessary for the release of endogenous CCK in response to food intake, particularly in the immediate postprandial period.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] Hildebrand et al 9 demonstrated that intraduodenal perfusion of a 30 g olive oil solution resulted in a threefold increase in plasma CCK concentrations from basal levels during the first postprandial hour that remained elevated for the remaining 4 h. In contrast, plasma CCK concentrations did not increase significantly during the experiment when Orlistat was administered. 9 Thus adequate digestion of dietary triglycerides by pancreatic lipase to produce FFAs is necessary for the release of endogenous CCK in response to food intake, particularly in the immediate postprandial period. As Orlistat inhibits lipolysis 9 and therefore reduces the appearance of FFAs in the small intestine, the release of CCK would be inhibited.…”

Section: Discussionmentioning

confidence: 99%

“…When administered intraduodenally, Orlistat also attenuated the CCK response to a triglyceride emulsion. 9,10 These studies therefore suggest that intragastric and intraduodenal administration of Orlistat attenuates CCK release, via its inhibitory effects on lipolysis. This attenuation may in turn modify CCK's functional capacity and its downstream effects on satiety, as observed by Matzinger et al,7 who demonstrated that intraduodenal administration of Orlistat inhibited CCK release and attenuated the reduction in food intake associated with intraduodenal fat perfusion.…”

Section: Introductionmentioning

confidence: 87%

“…Healthy nonobese subjects were included in the trial to allow for comparisons with studies that examined the effects of intragastric and intraduodenal, as opposed to oral, administration of Orlistat on physiological and behavioural satiety in healthy subjects. 7,[9][10][11][12] Obese subjects were also excluded from the trial to reduce any possible confounding effects of obesity on physiological and behavioural measures of appetite. 13,14 Experimental trial The subjects completed two randomised trials separated by 2 weeks, during which they ingested a test meal with Orlistat (120 mg) or placebo (2 g flour).…”

Section: Methodsmentioning

confidence: 99%

“…8 However, CCK is only released in response to adequate triglyceride hydrolysis by pancreatic lipase that increases intraduodenal long-chain FFA (4C10) concentrations. 7,[9][10][11][12] Both Borovicka et al 11 and Schwizer et al 12 demonstrated that intragastric administration of Orlistat with a stable emulsion of triglycerides (10% Intralipid), which reduced lipolysis by 75%, inhibited plasma CCK release. When administered intraduodenally, Orlistat also attenuated the CCK response to a triglyceride emulsion.…”

Section: Introductionmentioning

confidence: 99%

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Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

et al. 2003

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OBJECTIVE:To examine the short-term effects of a lipase inhibitor (Orlistat) on physiological and behavioural measures of appetite in response to a high-fat meal. DESIGN: Randomised, single blind, placebo-controlled, crossover trial. SUBJECTS: A total of 19 healthy nonobese male subjects. PROCEDURES: After an overnight fast, subjects ingested a test meal of 2940 kJ (60% fat, 30% CHO, 10% protein) with Orlistat (120 mg) or a placebo, separated by 2 weeks. Appetite, as assessed by a standard line scale, and plasma cholecystokinin (CCK) concentrations were measured prior to and every hour after the test meal for 4 h. Thereafter, subjects ingested a quantified, but self-selected portion of a standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final line scale questionnaire. RESULTS: The CCK response to the test meal was negatively correlated with BMI in both the Orlistat and placebo trials (R ¼ À0.69 and À0.65, Po0.01). Orlistat administration did not significantly alter the CCK response to the test meal (6.3073.27 vs 7.3673.94 pM min, for Orlistat and placebo, P ¼ 0.193). Similarly, the line scale measures of appetite and subsequent intake (5207205 vs 5547197 g, P ¼ 0.48) were not different between the trials. CONCLUSION: Orlistat administration did not alter short-term physiological or behavioural measures of satiety in response to a high-fat meal in healthy, nonobese subjects. The CCK response to a test meal may be partly determined by BMI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

et al. 2003

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Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects

et al. 2000

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The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.

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Physiology of Gastrointestinal Lipolysis and Therapeutical Use of Lipases and Digestive Lipase Inhibitors

Lengsfeld

Beaumier‐Gallon

Chahinian

et al. 2004

Lipases and Phospholipases in Drug Development

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Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release

Cited by 81 publications

References 24 publications

Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects

Physiology of Gastrointestinal Lipolysis and Therapeutical Use of Lipases and Digestive Lipase Inhibitors

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