Dopamine and Insulin Resistance

Vanderbilt University28 enrolled

Overview

Obese individuals have fewer striatal dopamine type 2 receptors (DRD2) than normal weight individuals. Lower DRD2 levels are associated with addiction and a decreased sense of pleasure.Obesity is also associated with insulin resistance (poor insulin action).We propose that insulin resistance and low DRD2 are associated. Using PET imaging,we aim to determine DRD2 binding potential (BP) in the brain is associated with insulin resistance and neuroendocrine hormone levels. Obese participants will be compared to lean, gender and age similar participants. We also aim to determine the effect of caloric restriction on DRD2 BP in obese subjects

In has been reported obese individuals have fewer striatal dopamine type 2 receptors (DRD2) compared to normal weight individuals congruent with diet induced obese rodent models and similar to models of addiction. Lower DRD2 levels are associated with addiction and a decreased sense of pleasure. Excessive weight gain also contributes to the onset of impaired insulin signaling (insulin resistance). In the brain insulin regulates monoamines and has trophic effects. We propose that the previous reports of low DRD2 in individuals with obesity will be associated with the degree of insulin resistance. Using PET imaging, we aim to determine DRD2 binding potential (BP) in the striatum and hypothesize these measurements will be associated with insulin resistance and potentially other neuroendocrine hormone levels. Obese participants will be compared to lean, sex and age similar participants. We also aim to determine the effect of caloric restriction on DRD2 BP in obese subjects. We hypothesize the caloric restriction will improve insulin resistance and that changes in DRD2 binding will be associated with changes in insulin signaling.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Obesity

Interventions

PET scanRADIATION

Both lean and obese undergo a PET scan of the brain using the radioligand,fallypride \[18F\] at baseline. Obese subjects who complete caloric restriction will have repeat scan after diet. Completed at baseline and post-VLCD

Oral glucose tolerance testPROCEDURE

Subjects will be required to drink a glucose solution; blood samples will be taken over a 5-hour time period Completed at baseline by both lean and obese and in obese post-VLCD

MRIPROCEDURE

An MRI of the brain and abdomen will be performed prior to PET scan One time at baseline in both lean and obese

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Ages 18-60 yrs * obese BMI \> 30kg/m2 and Weight less than 350 lbs * lean control BMI 18-25kg/m2 Exclusion Criteria: * Structured exercise \> equivalent to 30mins 5x week of walking times a week * History of Substance Abuse, including but exclusive to alcohol, cocaine, marijuana, heroin, nicotine * Current psychiatric disorder or significant h/o disorder * Use or any antidepressants or antipsychotics for last 3-6months or depot antipsychotics in the last 12 months * Any condition felt by PI or co-investigators to interfere with ability to complete the study * Inability to abstain from alcohol, physical exercise or \> 1 cup of coffee or equivalent daily for 3 days prior to imaging studies * Significant co-morbidities including atherosclerotic disease, metabolic disease, liver or renal insufficiency or abnormality found on MRI * Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning * Subjects on medications determined by PI, ex. sibutramine, frequent benzodiazepines or related drugs, which could affect quality of study for last 3 months.

Locations (1)

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Striatal DRD2 Receptor Binding

Region of interest compared to reference region to calculate binding potential

Time frame: Baseline and after 8-10days VLCD

Insulin

microU/ml