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 [18F]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/m2) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5–26.6 kg/m2). 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.
Highlights
Dysregulations of appetite, eating behavior and body weight are hallmark symptoms of a wide range of chronic and disabling illnesses that can collectively be referred to as food intake disorders (FID).[1]
cannabinoid 1 receptor (CB1R) availability was inversely correlated with log body mass index (BMI) in healthy subjects at a voxel-level threshold of PFWE-corrected o 0.05, but only in a few regions predominantly involved in the homeostatic regulation of body weight and energy balance
The psychobiological processes involved in eating behavior and body weight regulation are complex and incompletely understood,[41] but converging evidence points toward an important role of the neural circuits involved in the homeostatic and reward-related aspects of food intake, where the endocannabinoid system (ECS) has a vital role as neuromodulatory system.[42]
Summary
Dysregulations of appetite, eating behavior and body weight are hallmark symptoms of a wide range of chronic and disabling illnesses that can collectively be referred to as food intake disorders (FID).[1] In this sense, FID include obesity (OB) and eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN).[2,3] The core behavioral features of these disorders include either food avoidance or excessive food intake,[2] which may be accompanied by compensatory behavior (that is, fasting, excessive physical exercise, vomiting and/or laxative/diuretic use) intended to control weight (especially in AN and BN). Functional dyspepsia (FD), a prevalent functional gastrointestinal disorder characterized by meal-induced epigastric symptoms, is often accompanied by disturbed appetite and food intake as well as unintentional weight loss.[4] Together, these disorders represent major global health problems that put an enormous demand on health-care services, not at least because of their high medical comorbidity
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