Synergistic post-prandial deregulation of orexigenic and anorexigenic systems in obesity
B Gatta-Cherifi1,2, I Mattias1,3, M Vallée1,3, A Tabarin1,2, G Marsicano1,3, P V Piazza1,3 & D Cota1,3
Introduction: Obese humans have increased plasma levels of endocannabinoids like anandamide (AEA) and 2-arachydonoyl-glycerol (2-AG). However, it is unknown whether these orexigenic signals have a role in human eating behavior.
Design: We measured plasma AEA and 2-AG levels in 12 normal weight (10 F, age: 39.1±3.7 years, body mass index (BMI): 21.0±0.6 kg/m2, waist circumference (WC): 73.8±2.9 cm) and 12 insulin-resistant obese subjects (8 F, age: 37.4±3.4 years, BMI: 42.0±1.4 kg/m2, WC: 125.0±4.5 cm) 1 h before, immediately before and 1 h after the consumption of a balanced meal. The anorexigenic peptide YY (PYY) was measured at the same time points.
Results: Basal plasma AEA and 2-AG levels were increased in obese and positively correlated with BMI, WC and insulin for AEA. Before the meal, AEA similarly and significantly increased in both groups. After the meal, AEA decreased significantly in normal weight but not in obese subjects. 2-AG levels did not change over the meal. Post-prandial AEA change negatively correlated with WC and explained 20.7% of the variance observed for waist (r=0.455, r2=0.207, P=0.04). Likewise, post-prandial PYY change inversely correlated with WC and explained 21.3% of waist variance (r=0.462, r2=0.213, P=0.04). Post-prandial AEA and PYY changes were not correlated (r=0.242, P=0.30). A multiple regression analysis showed that post-prandial AEA and PYY changes explained 34% of the waist variance (r=0.582, r2=0.34, P<0.03), with only 8.2% of the variance commonly explained.
Conclusion: The pre-prandial peak of AEA suggests a role for this endocannabinoid in the initiation of the meal. The post-prandial changes of both the orexigenic AEA and the anorexigenic PYY are blunted in obese subjects and inversely and independently correlate with WC.