Neurohormonal & Behavioral Correlates of Obesity and Weight Loss

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 will be associated with a dysregulation of MOR system function, manifested by reductions in baseline MOR availability (binding potential, BP) in limbic and reward circuitry, and lower release of endogenous opioids after a standard meal, compared to lean volunteers. The latter is observed as acute reductions in the BP measure after meal ingestion.

Conditions

• Obesity

Interventions

DIETARY_SUPPLEMENT

Very Low Calorie Diet (VLCD)

Very Low Calorie Diet (VLCD) using the HMR meal replacement (Health Management Resources, Boston, MA). Typically, individuals consume 850-1000 kilocalories per day until a targeted 15% reduction in body weight is achieved.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• The Brain Research Foundation

  collaborator OTHER

• University of Michigan

  lead OTHER

Principal Investigators

• Paul R Burghardt, PhD · University of Michigan

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-02-28

Primary Completion

2013-01-15

Completion

2013-01-15

Countries

• United States

Study Locations