To explore whether obese adolescents with insulin resistance and relative low leptin levels exhibit functional alterations of the neuronal circuits involved in the regulation of energy metabolism and food seeking behaviors.

We here propose to test the hypothesis that the reward circuitry is dysregulated in obese adolescents and is related to the degree of insulin resistance and hyperinsulinemia.

Functional Magnetic Resonance Imaging (fMRI) provides a non-invasive method to assess the functional pathways affected by nutrient ingestion and therefore can help answer important questions regarding potential differences in the response of brain regions involved in feeding.

Inclusion Criteria:

• Obese adolescents
• Good general health,
• taking no medication on a chronic basis
• Age 12 to 17 yrs,
• in puberty (girls and boys: Tanner stage II - IV)

Obese Insulin Resistant Adolescents

• (BMI> 95th)
• (WBISI<1.2 plus a low adiponectin <6 ug/dl and
• high triglyceride levels >130mg/dl)

Obese Insulin Sensitive Adolescents

• (BMI>95th)
• (WBISI >3) plus high adiponectin >8 ug/ml and
• triglyceride levels > 80 mg/dl Girls who begin menstruating must have a negative pregnancy test during the study

Eligibility criteria for healthy non-obese children and adolescents:

• Brother or sister with obesity
• Age 12 to 17 years
• Normal fasting glucose and lipids in the child, and
• normal OGTT
• No use of any medication known to affect glucose, lipid metabolism and inflammation
• No endocrinopathies
• No use of any antipsychotic medication
• BMI >25th to <75th ( Center for Disease Control (CDC) BMI Charts)
• Minimum weight of 90lbs (CDC Growth Charts)

Exclusion Criteria

• Baseline creatinine >1.0 mg
• Pregnancy
• Presence of endocrinopathies (e.g. Cushing syndrome)
• Cardiac or pulmonary or other significant chronic illness
• Adolescents with psychiatric disorder or with substance abuse determined via self-report.
• Use of anorexic agents No metal implants

Clinic patients of Dr. Caprio at the Yale Pediatric Obesity Clinic who have undergone oral glucose tolerance testing (OGTT) and found to be insulin resistant or sensitive and/or previous research subjects who were found to be insulin resistant or sensitive and who agreed to be contacted for other studies will be contacted.