Neurohormonal & Behavioral Correlates of Obesity and Weight Loss

Study Summary

Obesity has reached epidemic levels in the United States, and is on the rise in many industrialized nations. The rate of recidivism for long-term weight loss is substantial and presents a critical problem given the importance of obesity as a modifiable risk factor for diseases like type 2 diabetes. Further, the comorbidity of depression with diseases like obesity, type 2 diabetes, and cardiovascular disease suggest that there may be an underlying shared biology for diseases of metabolic dysfunction and emotional dysregulation. The shared biology of these diseases may actually promote the precipitation and exacerbation of comorbid conditions, impacting the success of treatment. Endogenous opioid systems regulate a number of physiological and psychological processes including mood, energy management, and reward. Endogenous opioid µ-receptor-mediated reward processing is thought to be involved both in the short-term control of eating and hedonic food consumption, based on data in animal models. The present proposal will examine the function of the µ-opioid receptor (MOR) system in lean and obese human volunteers following an overnight fast and the change in µ-opioid receptor occupancy (i.e., endogenous opioid release) following the consumption of a standardized meal using PET imaging with the µ-selective radiotracer \[11C\]carfentanil. The obese individuals will be retested in the fasting and fed state following a 15% weight loss with a Very Low Calorie Diet. Further, the investigators will evaluate the function of the MOR system within the context of the individual's metabolic and psychological profile including aspects of mood and inhibitory control. This information will provide the neurobiological bases to develop novel avenues of intervention based on individual variations in central mechanisms associated with motivational systems and appetite and their potential role in weight regain. The investigators hypothesize that overeating in chronically obese individuals

Primary Outcome

\[11C\]carfentanil is a µ-opioid receptor selective radiotracer for PET imaging that will be used to asses the function of the µ-opioid receptor (MOR) system in the brains of lean and obese human volunteers. Measurements of \[11C\]carfentanil binding will be taken following an overnight fast and following the consumption of a standardized meal to determine the change in µ-opioid receptor occupancy (i.e., endogenous opioid release) in response to feeding.

Conditions Studied

Interventions

• DIETARY_SUPPLEMENT Very Low Calorie Diet (VLCD)

Study Locations (1)