Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers

Valerie L Darcey; Juen Guo; Meible Chi; Stephanie T Chung; Amber B Courville; Isabelle Gallagher; Peter Herscovitch; Rebecca Howard; Melissa LaNoire; Lauren Milley; Alex Schick; Michael Stagliano; Sara Turner; Nicholas Urbanski; Shanna Yang; Eunha Yim; Nan Zhai; Megan S Zhou; Kevin D Hall

doi:10.1101/2023.09.27.23296169

Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers

medRxiv [Preprint]. 2023 Sep 28:2023.09.27.23296169. doi: 10.1101/2023.09.27.23296169.

Authors

Valerie L Darcey^{1

2}, Juen Guo¹, Meible Chi¹, Stephanie T Chung³, Amber B Courville⁴, Isabelle Gallagher¹, Peter Herscovitch⁵, Rebecca Howard¹, Melissa LaNoire¹, Lauren Milley¹, Alex Schick¹, Michael Stagliano¹, Sara Turner⁶, Nicholas Urbanski¹, Shanna Yang⁶, Eunha Yim⁷, Nan Zhai¹, Megan S Zhou¹, Kevin D Hall¹

Affiliations

¹ Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
² Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, USA.
³ Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁴ Human Energy and Body Weight Regulation Core, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁶ Nutrition Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁷ University of Maryland, College Park, MD, USA.

Abstract

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [¹⁸F]fallypride and [¹¹C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m²). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [¹¹C]raclopride (r= -0.51; p<0.0001) but not [¹⁸F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [¹⁸F]fallypride has greater binding affinity to dopamine type-2 receptors than [¹¹C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.

Keywords: MRI; Obesity; PET; [11C]raclopride; [18F]fallypride; controlled-feeding; dopamine; striatum.

Publication types

Preprint