title: Oleoylethanolamide and human neural responses to food stimuli in obesity.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Case-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.
  
  
  METHODS
  Interactions 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
  This 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.
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Grosshans
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Schwarz
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Jan Malte
authors.initials: JM
authors.lastname: Bumb
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Rohleder
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Vollmert
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Vollstädt-Klein
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Tost
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
mesh_terms: D000328:Adult; D001069:Appetite Regulation / Q000502:physiology*; D001095:Arachidonic Acids / Q000097:blood / Q000502:physiology; D015992:Body Mass Index; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000502:physiology*; D066249:Craving / Q000502:physiology; D063388:Endocannabinoids / Q000097:blood / Q000502:physiology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D020738:Leptin / Q000097:blood / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D009829:Oleic Acids / Q000097:blood / Q000502:physiology*; D010775:Photic Stimulation; D053284:Polyunsaturated Alkamides / Q000097:blood; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D020738:Leptin; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; C078814:anandamide