Effect of AT-derived miRNA on the Biology and Insulin Sensitivity of Skeletal Muscle in Humans

Study Objectives:

• To establish and optimize the methodology for measuring adipose tissue miRNA release.
• To establish and optimize the methodology for measuring the effect of adipose tissue-released miRNA on skeletal muscle biology and insulin sensitivity.
• To profile adipose tissue-released miRNA in lean insulin-sensitive and obese insulin-resistant healthy individuals.
• 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