Introduction/Aims: Fat stimulates intestinal secretion of oleoylethanolamide (OEA) to reduce food intake, while fasting induces intestinal endocannabinoids with an orexigenic effect. Animal studies suggest that high-fat diet-induced obesity impairs intestinal control of endocannabinoid and OEA production, contributing to reduced satiety and weight gain. The aims of this study were to: (i) evaluate effects of intraduodenal (ID) lipid infusion on plasma levels of anandamide (AEA), 2-arachidonylglycerol (2-AG) and OEA in humans, and to examine relationships with BMI and ad libitum energy and fat intakes, and (ii) to evaluate effects of ID lipid on duodenal concentrations of 2-AG, AEA and OEA.
Methods: 19 lean, 16 overweight and 17 obese participants underwent ID Intralipid® infusion (2 kcal/min) for 120 min during which blood samples were collected every 30 min. Ad libitum energy intake was assessed at a subsequent buffet meal. Endoscopic duodenal biopsies were collected from 4 lean participants, at baseline, and following 30 min ID Intralipid® infusion (2kcal/min). Plasma and duodenal 2-AG, AEA and OEA concentrations were assessed by HPLC/tandem mass spectrometry
Results: There were positive relationships between fasting plasma 2-AG (r=0.4, P=0.009) and AEA (r=0.3, P=0.018), but not OEA, with BMI. ID lipid had no effect on plasma concentrations of 2-AG or AEA, but there was a group*time interaction for OEA (P=0.026). OEA increased in response to lipid in the obese, but not the lean or overweight groups (post-hoc P=NS). There was a relationship between plasma OEA at t=120 min with energy (r=0.35, P=0.022), but not fat, intake at the buffet meal. 30-min of ID fat infusion significantly increased duodenal OEA (P=0.046), but had no effect on 2-AG or AEA concentrations.
Conclusions: Fasting endocannabinoid tone, and lipid-induced OEA secretion appear altered in human obesity. Duodenal mobilisation of OEA may play an important role in the regulation of food intake.