Oleoylethanolamide and Human Neural Responses to Food Stimuli in Obesity

Abstract

IMPORTANCE Obesity has emerged as a leading health threat but its biological basis remains insufficiently known, hampering the search for novel treatments. Here, we study oleoylethanolamide, a naturally occurring lipid that has been clearly implicated in weight regulation in animals. However, its role for weight regulation and obesity in humans is still unclear.OBJECTIVE To investigate associations between plasma oleoylethanolamide levels and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and functional magnetic resonance imaging response to food stimuli in obese patients and matched control participants. DESIGN, SETTING, AND PARTICIPANTSCase-control study of 21 obese patients and 24 matched control participants. Obesity was defined as having a BMI of at least 30. The mean age of participants was 40.8 years and BMIs ranged from 18.2 to 47.5. MAIN OUTCOMES AND MEASURESInteractions between plasma oleoylethanolamide levels and obesity on BMI and functional magnetic resonance imaging response to food stimuli.RESULTS Associations between oleoylethanolamide and BMI differed significantly depending on whether individuals were obese or not (P = .02). In obese individuals, oleoylethanolamide showed a trend toward a positive correlation with BMI (P = .06, ρ = 0.42), while this relationship was inverse for nonobese control participants (P = .07, ρ = −0.34). Similarly, we found significant interactions between oleoylethanolamide levels and obesity on food-related brain activation in cortical areas associated with reward processing and interoceptive signaling (P = .009). Specifically, nonobese individuals with higher oleoylethanolamide levels had higher insular brain activity (P < .001, ρ = 0.70); again, the relationship trended to be inverse for obese patients (P = .11, ρ = −0.36). These effects were not associated with plasma levels of leptin and anandamide, suggesting an independent role of oleoylethanolamide in hunger-associated interoceptive signaling. Analysis of food craving during the functional magnetic resonance imaging task suggested that the identified brain areas may be involved in suppressing food-liking reactions in nonobese individuals. CONCLUSIONS AND RELEVANCEThis study suggests that oleoylethanolamide-mediated signaling plays an important role for hedonic regulation of food craving and obesity in humans and thus may be a valuable target for developing novel antiobesity drugs.

Eating disorders: from bench to bedside and back

“…Furthermore, a recent study suggested that OEA signaling has a crucial role for hedonic regulation of food craving and obesity in humans (Grosshans et al . ), and a previous report showed how this signal is altered in the blood and cerebrospinal fluid of women who suffered from bulimia and anorexia nervosa (Gaetani et al . ).…”

Dysfunctional oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome

“…Studies in a Norwegian population-based cohort have associated a single-nucleotide polymorphism in the gene encoding for NAPE-PLD , the enzyme responsible for the production of OEA, with severe obesity [39]. Furthermore, functional imaging experiments have suggested a role for OEA in the hedonic regulation of food craving and obesity in humans [40]. The present results show that deletion of the PWS-related gene, Magel2 , is accompanied by a paradoxical enhancement of food-induced OEA production in the jejunum, as well as by increased OEA levels in plasma.…”

The Endocannabinoid-Like Derivative Oleoylethanolamide at the Gut–Brain Interface: A “Lipid Way” to Control Energy Intake and Body Weight

“…A meal rich in oleic acid increases OEA plasma levels in healthy volunteers also reducing the total energy intake 3 hours after oleic acid ingestion [118]. In a recent study [132] on obese patients, it was found that plasma OEA levels positively correlated with body mass index (BMI) whereas an inverse correlation was observed between obesity andbrain areas activity (e.g., insula) associated with rewardsignaling. Chronic consumption of "obesogenic" high-fat food can dampen dopaminemediated signaling of reward and disrupt the relationship between palatable food-associated hedonic eating and neural correlates of reward processing [133][134][135].…”