Fat-induced heal brake in humans: A dose-dependent phenomenon correlated to the plasma levels of peptide YY

Pironi, Loris; Stanghellini, Vincenzo; Miglioli, M.; Corinaldesi, Roberto; Giorgio, Roberto De; Ruggeri, E; Tosetti, Cesare; Poggioli, Gilberto; Morselli-Labate, Antonio Maria; Monetti, Nino; Gozzetti, G; Barbara, L; Go, Vay Liang W.

doi:10.1016/0016-5085(93)90890-o

Cited by 186 publications

(91 citation statements)

References 21 publications

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“…Therefore, the satiating effect of ileal fat infusion was not dose dependent. In humans, Pironi et al 10 were the first to show a significant correlation between the dose of lipids administered to the ileum and the ileal brake effect on gastric emptying. Similarly, Keller et al 9 demonstrated that the ileal brake induced a dose-dependent inhibition of pancreatic and biliary secretion.…”

Section: Discussionmentioning

confidence: 99%

“…Pironi et al 10 found an increase in PYY release after ileal infusion of a small amount of 480 mg of fat (given as free fatty acids (FFA)). In this study, the amounts of lipids administered correlated with release of PYY.…”

Section: Discussionmentioning

confidence: 99%

“…9,10,38 PYY is released from L-endocrine cells of which the high concentrations in humans are found in the distal small intestine, colon and rectum, with progressively more PYY-producing cells when going distally in the gut. The most powerful stimulants for PYY release is fat, especially (triglycerides consisting of) long-chain fatty acids, although amino acids and even carbohydrates have been shown to be effective.…”

Section: Discussionmentioning

confidence: 99%

“…8 Long-chain fatty acids are potent triggers of the ileal brake, 5,7 and several studies have demonstrated that the ileal brake is already activated by small amounts of fat or free fatty acids. [9][10][11] However, it is not known whether these small amounts of fat are able to induce satiety and influence food intake. Evidence for a direct effect of the ileal brake on satiety and food intake in humans is limited to two publications from the same research group.…”

Section: Introductionmentioning

confidence: 99%

“…A second aim was to evaluate the effect of ileal lipid administration on gut peptide secretion, more specifically on cholecystokinin (CCK), as a more proximal gut peptide with well-known satiety effects, 13 and peptide YY, as a distal gut peptide and proposed biomarker for the activation of the ileal brake. 10 We constructed the following hypotheses: compared with oral ingestion of 3 g of lipid added to a liquid meal, delivery of the same amount of lipid through postprandial (after ingestion of the fat-free breakfast) perfusion into the ileum will (1) lead to an increase in postprandial satiety, (2) be dose dependent (9 g vs 3 g in the ileum) and (3) lead to distal gut hormone secretion.…”

Section: Introductionmentioning

confidence: 99%

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Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers

et al. 2008

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Objective: The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion. Design: Randomized, single-blind crossover design. Subjects: Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4). Intervention: Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t ¼ 105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment I3g) or 9 g (treatment I9g) fat (safflower oil). Measurements: Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY. Results: C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g (I3g and I9g) significantly increased satiety during and after fat perfusion, without differences in satiety between I3g and I9g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels. Conclusion: Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers

et al. 2008

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Short Bowel Syndrome and Small Bowel Transplantation

DiBaise

Sudan

2015

Yamada' S Textbook of Gastroenterology

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Glyco‐Scan: Varying Glycosylation in the Sequence of the Peptide Hormone PYY3‐36 and Its Effect on Receptor Selectivity

et al. 2010

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The increasing prevalence of obesity worldwide calls for safe and highly efficacious satiety drugs. PYY3-36 has been implicated in food intake regulation, and novel peptide analogues with high Y2 receptor-subtype selectivity and potency have potential as drugs for the treatment of obesity. It has been hypothesized that PYY3-36 associates with the plasma membrane prior to receptor activation such that the amphipathic alpha-helix of PYY3-36 possibly guides the C-terminal pentapeptide into the correct conformation for receptor activation. Ala-scans are used routinely to study the effect of individual amino acids in a given peptide sequence. Here we report the glyco-scan of the peptide hormone PYY3-36, in which hydroxyl side-chain functionalities were glycosylated; in addition new glycosylation sites were introduced. An array of novel PYY3-36 analogues with a glycan positioned in the water-membrane interface or in the N terminal were screened for Y-receptor affinity and selectivity as well as metabolic stability. Interestingly, in contrast to the Y1 and Y4 receptors, the Y2 receptor readily accommodated glycosylations. Especially glycosylations in the alpha-helical region of PYY3-36 were favorable both in terms of Y-receptor selectivity and endopeptidase resistance. We thus report several PYY3-36 analogues with enhanced Y-receptor selectivity. Our results can be used in the design of novel PYY analogues for the treatment of obesity. The glyco-scan concept, as systematically demonstrated here, has the potential for a wider applicability.

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Fat-induced heal brake in humans: A dose-dependent phenomenon correlated to the plasma levels of peptide YY

Cited by 186 publications

References 21 publications

Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers

Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers

Short Bowel Syndrome and Small Bowel Transplantation

Glyco‐Scan: Varying Glycosylation in the Sequence of the Peptide Hormone PYY3‐36 and Its Effect on Receptor Selectivity

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