Dopamine and Insulin Resistance
Condition: Obesity
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): PET scan; Oral glucose tolerance test; MRI; Psychological scales to assess attitudes and behaviors related to eating and quality of life; Caloric Restriction
Intervention type(s): Radiation; Procedure; Procedure; Behavioral; Other
Intervention description(s): 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; 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; An MRI of the brain and abdomen will be performed prior to PET scan One time at baseline in both lean and obese; A series of short psychological scales will be administered during the study. Completed at baseline; Obese participants only complete a short-term (~10days) very low calorie diet
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Lean who are age and sex similar to obese will complete baseline outcome measurements only.
Obese will complete baseline outcome measurements then the VLCD intervention with post outcome measurements .
Masking: None (Open Label)
Primary purpose: Other
Keywords: Obesity; Insulin Resistance; Neuroendocrine regulation; Eating behaviors; Dopamine signaling