Obesity is associated with decreased μ-opioid but unaltered dopamine D2 receptor availability in the brain.
Neurochemical pathways involved in pathological overeating and obesity are poorly understood. Although previous studies have shown increased μ-opioid receptor (MOR) and decreased dopamine D2 receptor (D2R) availability in addictive disorders, the role that these systems play in human obesity still remains unclear. We studied 13 morbidly obese women [mean body mass index (BMI), 42 kg/m(2)] and 14 nonobese age-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [(11)C]carfentanil and [(11)C]raclopride, respectively. We also used quantitative meta-analytic techniques to pool previous evidence on the effects of obesity on altered D2R availability. Morbidly obese subjects had significantly lower MOR availability than control subjects in brain regions relevant for reward processing, including ventral striatum, insula, and thalamus. Moreover, in these areas, BMI correlated negatively with MOR availability. Striatal MOR availability was also negatively associated with self-reported food addiction and restrained eating patterns. There were no significant differences in D2R availability between obese and nonobese subjects in any brain region. Meta-analysis confirmed that current evidence for altered D2R availability in obesity is only modest. Obesity appears to have unique neurobiological underpinnings in the reward circuit, whereby it is more similar to opioid addiction than to other addictive disorders. The opioid system modulates motivation and reward processing, and low μ-opioid availability may promote overeating to compensate decreased hedonic responses in this system. Behavioral and pharmacological strategies for recovering opioidergic function might thus be critical to curb the obesity epidemic.
Turku PET Centre, and lauri.nummenmaa@aalto.fi hekrka@utu.fi.
Henry K
HK
Karlsson
Turku PET Centre, and Departments of Psychiatry.
Lauri
L
Tuominen
Turku PET Centre, and.
Jetro J
JJ
Tuulari
Turku PET Centre, and Radiology.
Jussi
J
Hirvonen
Radiology.
Riitta
R
Parkkola
Turku PET Centre, and.
Semi
S
Helin
Surgery, and.
Paulina
http://orcid.org/0000-0001-6435-9264
P
Salminen
Turku PET Centre, and Endocrinology, Turku University Hospital, FI-20520 Turku, Finland, and.
Pirjo
P
Nuutila
Turku PET Centre, and Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, FI-00076 Aalto, Finland lauri.nummenmaa@aalto.fi hekrka@utu.fi.
Lauri
L
Nummenmaa
D000328:Adult; D019412:Anatomy, Cross-Sectional; D001923:Brain Chemistry / Q000502:physiology*; D004435:Eating / Q000523:psychology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009767:Obesity, Morbid / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D011795:Surveys and Questionnaires
D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu
dopamine; obesity; opioids; positron emission tomography; receptors; reward