Cerebral \u03bc-opioid and CB1 receptor systems have distinct roles in human feeding behavior

Tatu Kantonen,Kari Kalliokoski,Valtteri Kaasinen,Laura Pekkarinen,Pirjo Nuutila,Jussi Hirvonen,Lauri Nummenmaa,Tomi Karjalainen,Janne Isojärvi

doi:10.1038/s41398-021-01559-5

Tatu Kantonen, Kari Kalliokoski + Show 7 more

Open Access

https://doi.org/10.1038/s41398-021-01559-5

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Abstract

Eating behavior varies greatly between individuals, but the neurobiological basis of these trait-like differences in feeding remains poorly understood. Central μ-opioid receptors (MOR) and cannabinoid CB1 receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain’s opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2 scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating—individuals with low MORs reported being more likely to eat in response to environment’s palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically in brain regions regulating food reward, they have distinct roles in mediating individual feeding patterns. Central MOR system might provide a pharmacological target for reducing individual’s excessive cue-reactive eating behavior.

Highlights

Obesity is one of the leading public health issues, resulting from individuals’ long-term excessive energy intake in relation to energy expenditure [1]
We tested whether the mediated by μ-opioid receptor (MOR) and CB1 receptors (CB1R) availabilities in food-intakeregulating brain areas associate with individual eating behavior traits measured with Dutch Eating Behavior Questionnaire (DEBQ)
We identified all the [11C] carfentanil and [18F]FMPEP-d2 baseline positron emission tomography (PET) studies accompanied with completed Finnish version of the DEBQ form [41]

Summary

INTRODUCTION

Obesity is one of the leading public health issues, resulting from individuals’ long-term excessive energy intake in relation to energy expenditure [1]. Restrained eating refers to the tendency to eat less than desired [37,38,39] Variation in such trait-like feeding patterns contribute to differences in weight gain and maintenance [37, 40], and they can be measured using The Dutch Eating Behavior Questionnaire (DEBQ) [41]. In this retrospective study utilizing PET scans from historical healthy controls, we compiled 92 [11C]carfentanil scans of MOR system and 35 [18F] FMPEP-d2 scans of CB1R system and corresponding DEBQ scores. We tested whether the MOR and CB1R availabilities in food-intakeregulating brain areas associate with individual eating behavior traits measured with DEBQ

MATERIALS AND METHODS

RESULTS

CONCLUSIONS