The purpose of this study is to identify how certain parts of the brain that help control body weight respond to an infusion of hormones called leptin and amylin.

Following an overnight fast, subjects will undergo fMRI measurements of the hypothalamus, brainstem and whole brain during an infusion of either normal saline, pramlintide, leptin, or the combination leptin and pramlintide.

Inclusion Criteria:

• Age 18 year to 45 years of age
• MI 18 to 25 kg/m2 or ≥ 30 kg/m2
• At maximal lifetime weight
• Weight stable for at least 3 months

Exclusion Criteria:

• Those with a major medical illness or who require prescription medication, including: cancer, coronary artery disease, hypertension, and diabetes.

• Subjects taking psychiatric or centrally-acting (CNS) medications or who are diagnosed with a psychiatric or neurological illness, including:

  • depression
  • anorexia
  • bulimia
  • seizure disorder.

• Exercise > 30 minutes, 3 times a week

• Alcohol consumption > 2 drinks / day

• Weight > 350 lbs (159 kg) (weight limit for MR machine)

• Illicit drug use

• Pregnancy

• Extreme dietary habits as determined by a GCRC nutritionist: very high or low dietary carbohydrate or fat intakes

• Those with a contraindication to exposure to strong magnetic fields: presence of metal in the body such as body piercing, shrapnel, cardiac pacemakers or aneurysm clips

• Those with claustrophobia

• Anaphylaxis and known hypersensitivity to E. coli-derived proteins

• Allergies or contraindications to metreleptin or pramlintide

• Renal or hepatic impairment

• Women who are lactating

• Tobacco use