TY - JOUR
T1 - Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration
AU - Dunn, Julia P.
AU - Abumrad, Naji N.
AU - Kessler, Robert M.
AU - Patterson, Bruce W.
AU - Li, Rui
AU - Marks-Shulman, Pamela
AU - Tamboli, Robyn A.
N1 - Funding Information:
Funding agencies: JPD received support from the Vanderbilt Environmental Health Science Scholars Program (NIEHS K12 ESO15855) and Veterans Affairs Career Development Award (1IK2CX000943). This work was supported by NIH grant RO1-DK070860 to NNA; by the Vanderbilt CTSA grant 1 UL1 RR024975; the Vanderbilt Diabetes Research and Training Center (DK20593); REDCap database grant (UL1 TR000445); and the NIH Washington University Nutrition and Obesity Research Center (P30 DK56341). Disclosure: The authors declared no conflicts of interest. Clinical trial registration: ClinicalTrials.gov identifier NCT00802204. Additional Supporting Information may be found in the online version of this article Received: 30 May 2017; Accepted: 21 August 2017; Published online 25 September 2017. doi:10.1002/oby.22023
Publisher Copyright:
© 2017 The Obesity Society
PY - 2017/11
Y1 - 2017/11
N2 - Objective: It has been previously reported that early after Roux-en-Y-gastric bypass, dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BPND) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BPND and whether such changes are explained by neuroendocrine regulation. Methods: Fifteen females with obesity (BMI = 39 ± 6 kg/m2) were studied before and after ∼10 days of a very-low-calorie-diet (VLCD). Outcome measures included fasting insulin, leptin, acyl ghrelin, and glucose, and insulin sensitivity and disposition index were estimated using the oral-minimal model (OMM) method. Participants underwent positron emission tomography scanning with the displaceable radioligand [18F]fallypride to estimate available regional D2/3R levels. Regions of interest included the caudate, putamen, ventral striatum, hypothalamus, and substantia nigra (SN). Results: With the VLCD, weight decreased slightly (−3 kg). Insulin, glucose, and leptin decreased significantly, but there was no change in acyl ghrelin or measures from OMM. SN D2/3R BPND decreased significantly, with trends toward decreased levels in the remaining regions. The decrease in leptin concentration strongly predicted the change in D2/3R BPND in all regions (all P ≤ 0.004). Conclusions: In obesity, reductions in regional D2/3R availability after VLCD are suggestive of increased endogenous DA competing with the radioligand. Changes in regional D2/3R availability were associated with decreases in leptin concentrations that occurred before clinically significant weight loss.
AB - Objective: It has been previously reported that early after Roux-en-Y-gastric bypass, dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BPND) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BPND and whether such changes are explained by neuroendocrine regulation. Methods: Fifteen females with obesity (BMI = 39 ± 6 kg/m2) were studied before and after ∼10 days of a very-low-calorie-diet (VLCD). Outcome measures included fasting insulin, leptin, acyl ghrelin, and glucose, and insulin sensitivity and disposition index were estimated using the oral-minimal model (OMM) method. Participants underwent positron emission tomography scanning with the displaceable radioligand [18F]fallypride to estimate available regional D2/3R levels. Regions of interest included the caudate, putamen, ventral striatum, hypothalamus, and substantia nigra (SN). Results: With the VLCD, weight decreased slightly (−3 kg). Insulin, glucose, and leptin decreased significantly, but there was no change in acyl ghrelin or measures from OMM. SN D2/3R BPND decreased significantly, with trends toward decreased levels in the remaining regions. The decrease in leptin concentration strongly predicted the change in D2/3R BPND in all regions (all P ≤ 0.004). Conclusions: In obesity, reductions in regional D2/3R availability after VLCD are suggestive of increased endogenous DA competing with the radioligand. Changes in regional D2/3R availability were associated with decreases in leptin concentrations that occurred before clinically significant weight loss.
UR - http://www.scopus.com/inward/record.url?scp=85030478986&partnerID=8YFLogxK
U2 - 10.1002/oby.22023
DO - 10.1002/oby.22023
M3 - Article
C2 - 28944597
AN - SCOPUS:85030478986
VL - 25
SP - 1910
EP - 1915
JO - Obesity
JF - Obesity
SN - 1930-7381
IS - 11
ER -