title: Association between cerebral cannabinoid 1 receptor availability and body mass index in patients with food intake disorders and healthy subjects: a [(18)F]MK-9470 PET study.
abstract: Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12.5-40.6 kg/m(2)) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5-26.6 kg/m(2)). The association between regional CB1R availability and BMI was assessed within predefined homeostatic and reward-related regions of interest using voxel-based linear regression analyses. CB1R availability was inversely associated with BMI in homeostatic brain regions such as the hypothalamus and brainstem areas in both patients with FID and healthy subjects. However, in FID patients, CB1R availability was also negatively correlated with BMI throughout the mesolimbic reward system (midbrain, striatum, insula, amygdala and orbitofrontal cortex), which constitutes the key circuit implicated in processing appetitive motivation and hedonic value of perceived food rewards. Our results indicate that the cerebral homeostatic CB1R system is inextricably linked to BMI, with additional involvement of reward areas under conditions of disordered body weight.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Ceccarini
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Weltens
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.
authors.forename: H G
authors.initials: HG
authors.lastname: Ly
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.|Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Tack
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.|Liaison Psychiatry, University Psychiatric Center Campus Gasthuisberg, University Hospitals Leuven, Leuven, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.|Leuven Institute for Neurobiology and Disease, KU Leuven, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D000856:Anorexia Nervosa / Q000000981:diagnostic imaging* / Q000378:metabolism; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D052018:Bulimia Nervosa / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D054022:Cerebrum / Q000000981:diagnostic imaging / Q000378:metabolism; D004415:Dyspepsia / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D009765:Obesity / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D015431:Weight Loss; D055815:Young Adult
chemical_list: C571130:CNR1 protein, human; C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1