Elsevier

The Lancet

Volume 357, Issue 9253, 3 February 2001, Pages 354-357
The Lancet

Articles
Brain dopamine and obesity

https://doi.org/10.1016/S0140-6736(00)03643-6Get rights and content

Summary

Background

The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain.

Methods

Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG).

Findings

Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2·47 [SD 0·36]) than in controls (2·99 [0·41]; p<0·0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0·84; p⩾0·002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery.

Interpretation

The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.

Introduction

The prevalence of obesity is increasing worldwide, which has resulted in a significant increase in morbidity and mortality. Considerable efforts have been devoted to the development of weight-control medications that target neurotransmitters in the brain that regulate food intake.1 Several neurotransmitters (dopamine, GABA, norepinephrine, serotonin) as well as peptides and aminoacids are involved in the regulation of food intake.2 Of particular interest is dopamine since this neurotransmitter seems to regulate food intake3 by modulating food reward via the meso-limbic circuitry of the brain.4 In fact, drugs that block dopamine D2 receptors increase appetite and result in significant weight gain5 whereas drugs that increase brain dopamine concentration are anorexigenic.6, 7, 8

The involvement of dopamine in pathological eating and obesity is poorly understood. Studies in animals have shown that in genetically obese mice (ob/ob), dopamine agonists normalised body weight.9 In human beings, studies have shown a higher prevalence of the Taq 1 A1 allele for the dopamine D2 receptors, which is linked with lower amounts of dopamine D2 receptors10 in obese individuals.11 Studies have also shown that genetic variants of the human obesity gene, which predict the body mass index (BMI), interact with the dopamine D2-receptor gene.12 However, the involvement of brain dopamine D2 receptors in obesity has not been directly assessed.

The purpose of this study was to assess if there are differences in brain dopamine D2 receptors in severely obese individuals. The dopamine system was assessed with [C-11]raclopride (radiotracer that binds to dopamine D2 receptors13) with positron emission tomography (PET). In parallel, we also measured regional brain glucose metabolism in these individuals with PET and 2-deoxy-2[18F]fluoro-D-glucose (FDG).14

Section snippets

Study design

Written informed consent was obtained from each participant after the methodology of the experiment was fully explained. Studies were approved by the Institutional Review Board at Brookhaven National Laboratory.

Obese individuals were selected from a pool of people with a BMI greater than 40 kg/m2 who responded to an advertisement. All were initially screened by telephone and then assessed as outpatients and excluded if they had: (1) current or past psychiatric or neurological disease;(2) head

Results

Ten severely obese individuals (5 women and five men; mean age 38·9 [SD 7·3] years; age range 26–54 years; BMI range 42–60, mean 51·2 [SD 4·8] kg/m2; body weight 125–177 kg) were selected. The controls were three women and seven men (age range 25–45 years; mean 37·5 [SD 5·9] years; BMI range 21–28, mean 24·7 [SD 2·6] kg/m2; body weight 55–90 kg). The two groups had similar education (obese 14·5 [SD 2·3] years, controls 15 [2·8] years), social, and economic background. The BMI of obese

Discussion

We have shown that there is a lower dopamine D2 receptor availability in the striatum of obese individuals than in normal individuals. Moreover, in the obese individuals the D2 receptor measures were negatively correlated with their BMI. The results lead to an association between low D2 receptor amounts in obese individuals or a more-severe eating disorder and higher BMI. Low levels of dopamine D2 receptors have also been reported in individuals addicted to various types of drugs including

References (29)

  • T Baptista

    Body weight gain induced by antipsychotic drugs: mechanisms and management

    Acta Psychiatr Scand

    (1999)
  • G-J Wang et al.

    Behavior and cardiovascular effects of intravenous methylphenidate in normal subjects and cocaine abusers

    Euro Addict Res

    (1997)
  • KG Bina et al.

    Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob Mice

    Neuroendocrinology

    (2000)
  • EP Noble et al.

    Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

    Arch Gen Psychiatr

    (1991)
  • Cited by (1557)

    • Dopamine D2 receptors in WFS1-neurons regulate food-seeking and avoidance behaviors

      2024, Progress in Neuro-Psychopharmacology and Biological Psychiatry
    View all citing articles on Scopus
    View full text