Effect of Caloric Restriction on Fat Oxidation in Obese Men and Women (Magellan II)

The purpose of this study is to better understand the different ways our bodies burn fat which may be important for obesity, diabetes, and cardiovascular disease.

In this study the investigators will examine the hypothesis that overweight/obese individuals that are unable to meet target weight loss goals on a low calorie diet (LCD) are intrinsically less metabolically flexible than their weight-losing counterparts. The investigators expect that this 'inflexibility' will be characterized by impaired fat oxidation (as determined by indirect calorimetry) in response to caloric restriction. If this were the case, these subjects may represent a population of 'super-responders' likely to demonstrate a robust response to approaches to increase fat oxidation. The investigators will also measure lipid concentrations in skeletal muscle and liver by hydrogen 1 magnetic resonance (1H-MRS) to determine both the stability of these measurements as well as the magnitude of changes that can be seen during LCD.

Eligibility Criteria:
Inclusion Criteria:

* Male or female subjects between the ages of 18 and 55 years, inclusive
* Body Mass Index (BMI) 27-30 kg/m2, inclusive, with hypertension, controlled (\<140 / \<90) either by diet or medication.
* BMI 30-40 kg/m2, inclusive.
* An informed consent document signed and dated by the subject or a legally acceptable representative.
* Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (hypertension controlled (\<140 / \<90) either by diet or medication is acceptable), hepatic, psychiatric, neurologic, allergic, (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing), muscle disease, diabetes, or severe uncontrolled hypertension.
* Known hypersensitivity to phentermine, lidocaine, bupivicaine or any medication component of the study procedure.
* Presence of cardiac pacemaker, implanted cardiac defibrillator, or brain aneurysm clips.
* Any significant bleeding diathesis which could preclude recovery from the biopsy procedure. ASA, ibuprofen, and any other oral anti platelet agent will be discontinued at least 7 days prior to procedure.
* Abnormal CK as per site laboratory ranges.
* Subjects with either a medical history of or physical evidence of keloid scar formation upon physical examination.
* 12-lead electrocardiogram (ECG) demonstrating a clinically significant abnormality.
* Pregnant or nursing females or females less than 6 months postpartum from the scheduled date of collection.
* Participation in non-routine rigorous exercise (e.g., road races, heavy lifting, etc.) within one week prior to the muscle biopsy procedures.
* Presence of any condition in the investigator's opinion that may negatively affect subject safety or protocol adherence.
* Females of childbearing potential (any female except those with tubal ligation, hysterectomy, or absence of menses \> 2years) unwilling to use an approved method of contraception (condom, diaphragm, implantable uterine device (IUD) that does not release hormones).
* Prior participation in the Magellan I study at the Translational Research Institute for Metabolism and Diabetes.