Dataset Information

Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration.

ABSTRACT:

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 (BP_ND ) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BP_ND 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 [¹⁸ F]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 BP_ND decreased significantly, with trends toward decreased levels in the remaining regions. The decrease in leptin concentration strongly predicted the change in D2/3R BP_ND 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.

SUBMITTER: Dunn JP

PROVIDER: S-EPMC5718041 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration.

Dunn Julia P JP Abumrad Naji N NN Kessler Robert M RM Patterson Bruce W BW Li Rui R Marks-Shulman Pamela P Tamboli Robyn A RA

Obesity (Silver Spring, Md.) 20170925 11

<h4>Objective</h4>It has been previously reported that early after Roux-en-Y-gastric bypass, dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BP<sub>ND</sub> ) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BP<sub>ND</sub> and whether such changes are explained by neuroendocrine regulation.<h4>Methods</h4>Fifteen females with obesity (BMI = 39 ± 6 kg/m<sup>2</sup> ) were studied before and ...[more]

PMID: 28944597

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Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1 and PPARto wild type levels; CR paradoxically further suppressed cardiac PPAR. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction. 6 month aged ob/ob mice were either leptin repleted with osmotic mini-pumps, calorie restricted to match the caloric intake of the leptin repleted mice, or fed ad lib for one month. 6-8 month C57Bl/6J mice were aged to serve as controls.

Dataset Information

Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration.

Objective

Methods

Results

Conclusions

Publications

Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration.

Similar Datasets

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