title: Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum.
abstract: Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [(11) C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, 12 in the [(11) C]PHNO PET study, 8 of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability. Using [(11) C]PHNO and PET brain imaging techniques we show that body mass index was positively associated with D2R/D3R availability in the dorsal striatum, but that functional MR BOLD response was unrelated to D2R/D3R availability. These results suggest the existence of a nonlinear relationship between D2R/D3R availability and body mass index and that the altered BOLD responses to food consumption seen in obesity are not directly related to D2R/D3R availability.
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Diagnostic Radiology, Yale PET Center, Yale University School of Medicine, New Haven, Connecticut.
authors: Kelly P
authors: KP
authors: Cosgrove
authors: Maria G
authors: MG
authors: Veldhuizen
authors: Christine M
authors: CM
authors: Sandiego
authors: Evan D
authors: ED
authors: Morris
authors: Dana M
authors: DM
authors: Small
mesh_terms: D000328:Adult; D000344:Afferent Pathways / Q000502:physiology; D015992:Body Mass Index; D003342:Corpus Striatum / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010078:Oxazines / Q000493:pharmacokinetics; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D013268:Stimulation, Chemical; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide; D010100:Oxygen
keywords: BMI; BOLD; PET; [11C]-(+)-PHNO; dopamine D2/3 receptor; fMRI; human