Neuromolecular Risk Factors for Obesity (PROSPECT)

The goal of this project is to characterize the neural and psychological mechanisms that contribute to development of obesity in the early adulthood. We address the neuromolecular risk factors for obesity using multi-modal molecular (positron emission tomography with) and functional (functional magnetic resonance imaging) neuroimaging in a prospective design. Normal weight adolescents with high versus low familial, genetic and psychological risk factors for obesity will be studied and followed for five years.

Diet, nutrition, and physical exercise are critical factors in the maintenance of good health through the entire life course. However, in most western countries the annual increase in the prevalence and the severity of obesity and physical inactivity is substantial. Early detection of individuals with high risk for obesity is important, because reversing the obese state is very difficult. To prevent and treat obesity, it is necessary to characterize neural mechanisms supporting altered incentive motivation and food intake, and to build a comprehensive model of the interactions between neural, physiological, and psychological factors contributing to development and maintenance of obesity. This obviously calls for novel data analysis techniques allowing fusion analysis of neurobiological, physiological, and behavioural data, as well as screening the critical combination of biomarkers for obesity.

A total of sixty males (30 normal-weight, 30 with risk for developing obesity) are recruited into this prospective study. The subjects will undergo physical examination, physical fitness tests, physical activity measures, body tissue composition measurement, structural and functional magnetic resonance imaging of the brain and body (MRI \& fMRI), and positron emission tomography (PET) with ligands \[18F\]-fluorodeoxyglucose (\[18F\]-FDG), \[18-F\]FMPEP, and \[11C\]carfentanil. Subjects' weight and physical condition will be followed up for 5 years.

In three interconnected work packages (WPs) we test three hypotheses derived from human and animal studies:

1. Altered reward and cognitive control functions in the brain predisposes some individuals to overeating and obesity.
2. Opioid system and reward circuit function provide feasible biomarkers for obesity risk.
3. Mobile tracking and behavioural paradigms tapping reward learning and inhibitory control can be used for unobtrusive and inexpensive detection of risk factors for obesity.

These studies will improve our understanding of the neural and psychological mechanisms of obesity and addictive disorders. This knowledge will translate into crucial knowledge for developing novel risk factor screening procedures, and novel pharmacological and psychological treatments for obesity.

Eligibility Criteria:
Inclusion Criteria:

Inclusion criteria for low-risk group:

* Male sex
* Age 20-35 years
* BMI 20-24 kg/m2
* Physical exercise \> 4 hrs per week
* No maternal / paternal obesity OR maternal / paternal type 2 diabetes mellitus (T2DM)

Inclusion criteria for high-risk group:

* Male sex
* Age 20-35 years
* BMI 25 - 30 kg/m2
* Maternal / paternal obesity OR maternal / paternal T2DM
* Physical exercise \< 4 hrs per week

Exclusion Criteria:

* Any chronic disease or medication that could affect glucose metabolism or neurotransmission
* History of anorexia nervosa, bulimia or other eating disorder (excl. common obesity)
* Smoking of tobacco, taking of snuffs, or use of narcotics
* Abusive use of alcohol
* Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results