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

Study Objectives:

1. 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.

2. 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.

3. 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)