title: Argument for a non-linear relationship between severity of human obesity and dopaminergic tone.
abstract: Alterations in the dopaminergic system have been implicated in both animal and human obesity. However, to date, a comprehensive model on the nature and functional relevance of this relationship is missing. In particular, human data remain equivocal in that seemingly inconsistent reports exist of positive, negative or even no relationships between dopamine D2/D3 receptor availability in the striatum and measures of obesity. Further, data on receptor availability have been commonly interpreted as reflecting receptor density, despite the possibility of an alternative interpretation, namely alterations in the basal levels of endogenous dopaminergic tone. Here, we provide a unifying framework that is able to explain the seemingly contradictory findings and offer an alternative and novel perspective on existing data. In particular, we suggest (i) a quadratic relationship between alterations in the dopaminergic system and degree of obesity, and (ii) that the observed alterations are driven by shifts in the balance between general dopaminergic tone and phasic dopaminergic signalling. The proposed model consistently integrates human data on molecular and behavioural characteristics of overweight and obesity. Further, the model provides a mechanistic framework accounting not only for the consistent observation of altered (food) reward-responsivity but also for the differences in reinforcement learning, decision-making behaviour and cognitive performance associated with measures of obesity.
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.|Department Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: A
authors.identifier: http://orcid.org/0000-0001-6184-8484
authors.initials: A
authors.lastname: Horstmann
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: W K
authors.initials: WK
authors.lastname: Fenske
authors.affiliation: IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: M K
authors.initials: MK
authors.lastname: Hankir
mesh_terms: D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials; D009434:Neural Pathways; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D059227:Postsynaptic Potential Summation; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012201:Reward
chemical_list: C493593:DRD3 protein, human; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D050637:Receptors, Dopamine D3; D004298:Dopamine
keywords: Dopamine; PET; obesity; reward sensitivity