Investigating Sex Differences in Mitochondrial Function and Leg Blood Flow During Exercise

This study will compare mitochondrial function and leg blood flow during exercise in healthy endurance-trained females and males aged 19-35. Participants will complete five laboratory visits over 2-3 weeks, including cycling and single-leg knee extension exercise tests, a dual-energy X-ray absorptiometry (DXA) body composition scan, one resting thigh muscle biopsy, ultrasound blood-flow measurements, muscle oxygen and activity measurements, intramuscular pressure measurement, OMNI perceived exertion ratings, and a finger-prick hemoglobin sample. The study will examine whether sex-related differences in muscle energy use, muscle torque, and muscle pressure help explain blood-flow delivery during exercise.

• Exercise (Other): Exercise - Men
• Exercise (Other): Exercise - Females

Primary outcomes

• Isolated mitochondria maximal state 3 respiration (pmols O2/microgram) measured via an ouroborous oxygraph (mitochondrial respirometry) [Baseline]: This measure quantifies the maximal rate of oxygen consumption (picomoles O2/ micogram of mitochondrial protein) when ADP, Malate, Succinate, Pyruvate and Glutamate have all been addded to the chamber.
• Maximal state 3 respiration in permeabilized Fibers (pmols O2/mg) measured via an ouroborous oxygraph (mitochondrial respirometry) [Baseline]: This measure quantifies the maximal rate of oxygen consumption (picomoles O2/ milligram of muscle tissue) when ADP, Malate, Succinate, Pyruvate and Glutamate have all been added to the chamber.
• Fiber type 1 specific maximal state 3 respiration (pmols O2/mg) measured via an ouroborous oxygraph (mitochondrial respirometry) [Baseline]: This measure quantifies the maximal rate of oxygen consumption (picomoles O2/ micogram of mitochondrial protein) when ADP, Malate, Succinate, Pyruvate and Glutamate have all been added to the chamber.
• Fiber type 2 specific maximal state 3 respiration (pmols O2/mg) measured via an ouroborous oxygraph (mitochondrial respirometry) [Baseline]: This measure quantifies the maximal rate of oxygen consumption (picomoles O2/ micogram of mitochondrial protein) when ADP, Malate, Succinate, Pyruvate and Glutamate have all been addded to the chamber.

Sex: All, ages: 19 Years to 35 Years, accepts healthy volunteers

Inclusion Criteria:

* can understand and communicate in English;
* are 19 to 35 years old;
* answer "No" to all questions on the Canadian Society for Exercise Physiology Get Active Questionnaire (CSEP-GAQ), or have approval from a doctor to do maximal exercise testing;
* are healthy enough to do hard exercise;
* are an endurance athlete; and
* have done at least 6 hours per week of planned endurance training, such as running, cycling, swimming, or rowing, over the past 12 months.

Exclusion Criteria:

* • currently use cigarettes, vaping products, or other nicotine products, or have used them in the past 2 years;

  * have a major uncontrolled heart, blood vessel, muscle, metabolic, or nervous system condition
  * have a medical condition that makes maximal exercise unsafe for you
  * have heart or lung disease, or a condition that affects your heart, lungs, blood vessels, or muscles
  * have type 1 or type 2 diabetes
  * have cancer or have had cancer treatment in the past 12 months
  * take blood-thinning medicine or have a bleeding disorder
  * are allergic to lidocaine or other local freezing medicine
  * are pregnant, think you may be pregnant, or are trying to become pregnant
  * are unable to follow the study instructions safely

• Results publication: Cardinale DA, Larsen FJ, Schiffer TA, Morales-Alamo D, Ekblom B, Calbet JAL, Holmberg HC, Boushel R. Superior Intrinsic Mitochondrial Respiration in Women Than in Men. Front Physiol. 2018 Aug 17;9:1133. doi: 10.3389/fphys.2018.01133. eCollection 2018. PMID 30174617