The purpose of this study is examine the effect of fat tissue-released miRNA on skeletal muscle and if abnormal fat tissue-released miRNA contributes to insulin resistance in obese individuals. This information will be important for our understanding of how the body's sugar metabolism is regulated and why people who are obese become insulin resistant and are more likely to develop type 2 diabetes.

Study Objectives:

1. To establish and optimize the methodology for measuring adipose tissue miRNA release.
2. To establish and optimize the methodology for measuring the effect of adipose tissue-released miRNA on skeletal muscle biology and insulin sensitivity.
3. To profile adipose tissue-released miRNA in lean insulin-sensitive and obese insulin-resistant healthy individuals.
4. To examine the effects of adipose tissue-released miRNA from lean insulin-sensitive individuals and obese insulin-resistant individuals on skeletal muscle biology and insulin sensitivity.

Inclusion Criteria:

• Able to communicate meaningfully with the investigator and legally competent to provide informed written consent
• 18-65 years of age
• BMI of 20-25 kg/m2 (lean subjects); 30-35 kg/m2 (obese subjects)
• Stable body weight (< 3 kg change in the last 8 weeks)
• homeostatic model assessment (HOMA)-insulin resistance <2.7 if lean; homeostatic model assessment (HOMA)-insulin resistance ≥2.7 if obese

Exclusion Criteria:

• Lactation or pregnancy, current and/or within last 6 months, per participant's report
• Female subjects postmenopausal
• Cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months)
• Liver disease (AST or ALT(alanine aminotransferase)>2.5 times the upper limit of normal)
• Kidney disease (creatinine >1.6 mg/dl)
• Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women)
• Thyroid dysfunction (abnormal TSH)
• HbA1c ≥6.5%
• Uncontrolled hypertension (systolic BP>160 mmHg, diastolic BP>100 mmHg)
• History of coagulopathies
• History (within the last 5 years) or presence of malignancy, (skin cancers, with the exception of melanoma, may be acceptable)
• Current or history of drug abuse or alcohol abuse (>2 drinks/day)
• Prior treatment (within last 3 months) with systemic glucocorticoids (>2 weeks), beta-blockers, drugs for weight loss, niacin or fibrates
• History of HIV, active Hepatitis B or C, or Tuberculosis (participant reported)
• Smoke > 5 cigarettes per day

Healthy obese insulin-resistant individuals Healthy lean insulin-sensitive individuals