The identification of intermittent fasting as an alternative method to traditional weight maintenance protocols could have a significant impact on preventing body weight regain common after successful weight loss, and potentially lead to a reduction in pharmaceutical and clinical costs related to the care of overweight and obese adults.

The research will examine the impact of intermittent fasting to promote long term body weight maintenance following successful weight loss in overweight and obese Veterans. This research is especially relevant to the majority of Veterans who struggle with obesity and maintaining weight loss. Obesity increases the risk for storing excess calories in ectopic depots, including skeletal muscle. Intramuscular fat is related to altered substrate utilization (metabolic inflexibility) and defects in insulin sensitivity, ultimately leading to type 2 diabetes mellitus and cardiovascular disease. The objective of this proposal is to test in a randomized clinical trial the effectiveness of an intensive weight management program with and without intermittent fasting (IF) to combat weight regain and the obesity crisis in our Veterans. Further, this application proposes to examine the role of several enzymes involved in skeletal muscle fatty acid oxidation as a mechanism for efficacious long term weight management.

Inclusion Criteria:

• Veteran
• 50-75 years of age
• BMI: 25-40 kg/m2
• Postmenopausal status for women

Exclusion Criteria:

• Uncontrolled diabetes (HbA1c >10% or the current use of insulin)
• Neurologic, musculoskeletal, or other condition that limits subject's ability to complete study physical assessments
• Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and psychiatric disease
• Weight change within the past month of >5 kg
• Self-reported alcohol or drug abuse
• Anti-coagulant medication for muscle biopsies only Impaired renal function (creatinine > 1.5 mg/dl) History or evidence of serious liver disease (LFTs > 2.5 x WNL)