The Investigational Weight Management Clinic now entitled the Weight Management Program at the University of Michigan was created to identify strategies that will result in cost-effective, long term weight management for overweight and obese individuals. The driving hypothesis of the clinic is that the 'one size fits all' philosophy is untenable with a complex disease such as obesity. The clinic will serve as a portal for patients to choose standard clinical care or to explore alternatives from a variety of clinical studies offered through the clinic. These studies will include further investigations into nutrition, the biological basis of weight and weight management and protocols using approved and experimental pharmaceuticals as well as technologies that aid in self-management of weight.

Inclusion Criteria:

• Obese males and females: age >20 years; Obese population defined as BMI > or = 27 kg/m2
• Lean population BMI < 27 but > 17 kg/m2
• Able and willing to provide written informed consent for the trial

Exclusion Criteria:

• Evidence of inherited disorders of lipid metabolism.
• History of Cancer within the last 5 years
• Human immunodeficiency virus (HIV) antibody positive.
• Patients with solid organ transplants.
• Participation in any other clinical trial within 90 days of entry into this trial.
• Pregnant or lactating females.
• Uncontrolled thyroid disease
• Unstable angina or NY heart association class II failure or above
• Gastrointestinal disease specifically GI motility disorders
• Unstable neuropsychiatric disease including major depression/anxiety, eating disorder such as binge eating, bulimia or anorexia
• End stage renal or hepatic disease
• Autoimmune disorders (e.g. SLE)
• Body weight fluctuation of more than 5 kg in the previous 3 months
• Prior bariatric surgery
• A history or current alcohol/substance abuse and change in smoking habits or cessation in the past 6 months.
• Women of childbearing age must use a reliable form of contraception.
• Any medical condition, which in the opinion of the investigator would make the patient unsuitable for recruitment, or could interfere with the patient participating in or completing the protocol.
• Unwilling or unable to consent for the study.

3000 obese participating in a 2 year clinical weight loss and weight maintenance program and 200 lean controls may opt-in to participate in a number of evaluations including depression inventory and HRQOL questionnaires, assessing hunger and appetite, work performance (including presenteeism and absenteeism), pain survey, oral glucose tolerance testing, mixed meal tolerance testing with metabolomics, DNA, RNA, with or without muscle and adipose tissue biopsies, body composition by DEXA or BodPod, measurements of REE and V02 max before at baseline, at 10-15% weight loss and after the 2 year clinical program.