BACKGROUND: Ileal delivery of fat reduces hunger and food intake through activation of the ileal brake. Physicochemical properties of fat have been shown to affect satiety and food intake. OBJECTIVE: The objective of this study was to assess the effect of ileal fat emulsions with differing degrees of fatty acid saturation on satiety, food intake, and gut peptides (cholecystokinin and peptide YY). We hypothesized that long-chain triacylglycerols with diunsaturated fatty acids would increase satiety and reduce energy intake compared with long-chain triacylglycerols with monounsaturated or saturated fatty acids. DESIGN: We performed a double-blind, randomized, crossover study in which 15 healthy subjects [mean age: 24 y; mean body mass index (in kg/m(2)): 22] were intubated with a naso-ileal catheter and participated in 4 experiments performed in random order on 4 consecutive days. After consumption of a liquid meal, subjects received a fat or control infusion in the ileum. Fat emulsions consisted of 6 g of 18:0 (shea oil; mainly 18:0), 18:1 (canola oil; mainly 18:1), or 18:2 (safflower oil; mainly 18:2) oils. Food intake was measured during an ad libitum lunch. Satiety questionnaires (visual analogue scale) and blood samples were collected at regular intervals. RESULTS: Compared with the control, only 18:2 and 18:1 significantly increased fullness and reduced hunger. No effect on food intake was observed. 18:1 and 18:2 increased cholecystokinin secretion significantly compared with the control. Fatty acid saturation did not affect peptide YY secretion. CONCLUSIONS: When infused into the ileum, triacylglycerols with unsaturated fatty acids increase satiety, whereas triacylglycerols with saturated fatty acids does not. This trial was registered with the Dutch Trial Register as ISRCTN51742545.