Associations between dopamine D2 receptor availability and BMI depend on age

Abstract

Objective The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects’ ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese. Subjects 130 healthy subjects between 18 and 81 years old underwent PET with [18F]falllypride, a high affinity DRD2/3 ligand. Results As expected, DRD2/3 availability declined with age. Critically, age significantly interacted with DRD2/3 availability in predicting BMI in the midbrain and striatal regions (caudate, putamen, and ventral striatum). Among subjects under 30 years old, BMI was not associated with DRD2/3 availability. By contrast, among subjects over 30 years old, BMI was positively associated with DRD2/3 availability in the midbrain, putamen, and ventral striatum. Conclusion The present results are incompatible with the prominent dopaminergic hypofunction hypothesis that proposes that a reduction in DRD2/3 availability is associated with increased BMI, and highlights the importance of age in assessing correlates of DRD2/3 function.

Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age

“…Both data sets (Study 1 and Study 2) were collected as part of large‐scale multimodal neuroimaging projects focused on decision making. Subsets of the Study 1 behavioral (Seaman et al, ), fMRI (Seaman et al, ) and PET (Dang et al, ; Dang et al, ; Smith et al, ) data were previously included in other publications. Specifically, age effects on D2‐like BP ND in a subset of Study 1 participants were reported or noted in three previous publications (Dang et al, ; Dang et al, ; Smith et al, ).…”

“…Subsets of the Study 1 behavioral (Seaman et al, ), fMRI (Seaman et al, ) and PET (Dang et al, ; Dang et al, ; Smith et al, ) data were previously included in other publications. Specifically, age effects on D2‐like BP ND in a subset of Study 1 participants were reported or noted in three previous publications (Dang et al, ; Dang et al, ; Smith et al, ). However, these were limited to non‐PVC striatal ROIs (Dang et al, , ) or very large cortical ROIs (i.e., frontal cortex, parietal cortex) that averaged across all gyri within a lobe (Smith et al, ).…”

Dopamine Adaptations as a Common Pathway for Neurocognitive Impairment in Diabetes and Obesity: A Neuropsychological Perspective

“…There are consistent findings in the animal literature that HFD, and adiposity alter DA signaling at the cellular, and molecular levels (Anderzhanova et al, 2007; Johnson and Kenny, 2010; van de Giessen et al, 2012, 2013; Sharma and Fulton, 2013; Tellez et al, 2013; Cansell et al, 2014; Adams et al, 2015; Woods et al, 2016), as well as mounting evidence for altered DA signaling in human obesity, especially reflected in changes in DA receptor density, (Wang et al, 2001, 2011; Dunn et al, 2010; Steele et al, 2010; Eisenstein et al, 2013, 2015; Guo et al, 2014; Cosgrove et al, 2015; Horstmann et al, 2015; Karlsson et al, 2015; Caravaggio et al, 2015b; Dang et al, 2016; Gaiser et al, 2016). Additionally, there is evidence that central and peripheral insulin resistance might impact DA function.…”

Sensory functioning in older adults: relevance for food preference

“…Interestingly, taste and reward networks can be altered by overweight and obesity, increasing problems in the population as a whole and particularly in middle aged and aging adults. Greater activation to consumption of sweet stimuli is seen in primary taste cortex in obese subjects; whereas, reduced activation has been observed in the reward areas of nucleus accumbens and the caudate 34,35,36 .…”

“…Older adults and obese subjects have reduced dopamine response and thus, are at particularly high risk for reward deficiency syndrome 34,35,36 . Food reward and taste are important motivators of diet and food consumption 37 , thus reward deficiency syndrome can lead to increased intake of rewarding stimuli, like sweet and fat tasting foods.…”