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

The purpose of this study is to collect data to help researchers identify factors, such as certain proteins or genetic codes, that are secreted from muscle that are associated with the beneficial effects of exercise.

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.

Eligibility Criteria:
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)