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=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.International Journal of Obesity advance online publication, 16 September 2008; doi:10.1038/ijo.2008.166.