Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation (Columbus)

Study Objectives:

• To identify specific changes in messenger ribonucleic acid (mRNA)/micro ribonucleic acid (miRNA) expression in muscle associated with higher or lower relative measures of mitochondrial capacity and fat oxidation.
• To identify secreted factors/miRNAs that specifically relate to the metabolic response of muscle and that are present after a single initial bout of exercise.
• To collect the appropriate clinical samples (muscle and adipose tissue, plasma/serum) to enable validation of myokines associated with changes in oxygen consumption/mitochondrial content via in vivo and in vitro discovery efforts.

Inclusion criteria

Applicable to all Groups

• Healthy men and women, aged 18 - 40, inclusive.
• Willing to stop alcohol and caffeine consumption for 48 hours preceding each blood draw

Applicable to Group 1

• BMI between 22 and 29.9 kg/m2
• Not involved in regular exercise program
• Willing to exercise every day for the study period

Applicable to Group 2

• BMI between 22 and 29.9 kg/m2
• Maximal oxygen uptake (VO2max) ≥ 45 ml/kg fat-free mass

/min

• Engaged in a minimum of 1.5 h of moderate to vigorous intensity aerobic exercise 3 times/ week

Applicable to Group 3

• BMI ≥ 30 kg/m2 and weight ≤ 350 lbs
• Not involved in a regular exercise program

Exclusion criteria

Applicable to All Groups

• History of Type 2 Diabetes
• "Unfavorable anatomy" for continuous venous blood sample collection
• Abnormal resting ECG
• Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp < 140/90 on medications)
• Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
• Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
• New onset (<3 months on a stable regime) use of oral contraceptives or hormone replacement therapy
• Alcohol or other drug abuse
• Smoking within the past 3 months
• Females that are currently or have been pregnant or are currently or have nursed a child within the last 12 months (minimum).
• Parental enrollment into the study that compromises the well being of the child [no partner or connected caregiver]
• Unwilling or unable to abstain from caffeine or alcohol 48 hours prior to metabolic rate measurements
• Increased liver function tests
• Metal objects that would interfere with the measurement of body composition /magnetic resonance spectroscopy such as implanted rods, surgical clips, etc
• Any New York Heart Association class of congestive heart failure
• History of deep vein thrombosis or pulmonary embolism
• Significant varicose veins
• Abnormal blood count/Anemia, or blood donation within the last 2 months
• Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
• Bariatric surgery or liposuction within the previous 3 years
• Cancer (active malignancy with or without concurrent chemotherapy)
• Rheumatoid disease
• Bypass graft in limb
• Known genetic factor (Factor V Leiden, etc) or hypercoagulable state
• Diagnosed peripheral arterial or vascular disease, or intermittent claudication
• Family history of primary deep vein thrombosis or pulmonary embolism
• Peripheral neuropathy
• Claustrophobia
• Frequent nocturnal urination and/or sleep apnea
• Presence of any condition that, in the opinion of the investigator, compromises participant safety or data integrity or the participants' ability to complete the training protocol

Applicable to Group 2

• Gait problems
• Major Depression
• Presence of an eating disorder or eating attitudes/behaviors that could interfere with the study completion
• Unwilling or unable to complete the protocol

Applicable to Group 3

• HbA1c ≥ 6.5% (O)