Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycelides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (B MI) of 51.0 kg/m(2) (range of 47.9-69.0)] and 10 men without obesity [BMI of 24.6 kg/m(2) (range of 21.7-26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TO) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids (P < 0.001). accelerated orocoecal transit lime (OCTY; p= 0.005), increased postload cholecystokinin section (P < 0.001), and suppressed ad libitum energy intake (P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group x lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMET(lipid) P = 0.046; GMET(water)( )P = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated (P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. however, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion. NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.