The effects of single leg immobilization on muscle protein synthesis, protein breakdown, and glucose uptake in healthy young men

Periods of muscle disuse are commonly experienced in young and elderly individuals as a result of short-term hospitalization or leg casting after injury. Periods of immobilization result in a profound loss of muscle mass and strength. Aside from skeletal muscle’s central role in movement, the muscle also plays a large role in general health. For example, skeletal muscle is the largest ‘sink’ into which blood sugar (glucose) is taken up following a meal. Leg immobilization results in an impairment in the body’s ability to take up glucose into skeletal muscle tissue, which can eventually result in insulin resistance. In our study, we are interested in looking at the regulation of muscle mass during and after a short period of leg immobilization. We will measure the rate of muscle growth and breakdown as well as the rate of glucose uptake by the muscle. Understanding the underlying mechanisms causing muscle loss after immobilization will help us to create interventions to prevent the loss of muscle mass and function during periods of disuse.

Single leg immobilization affects muscle protein synthesis, breakdown, and glucose uptake

After 3 d immobilization

Pre and Post 3 d immobilization

Day 0

Upon arrival to the laboratory in the fasted state, a saliva and blood sample will be taken. Participants will then ingest heavy water that allows for measuring integrated muscle protein synthesis rates. Two hours after ingestion of the heavy water another sample of saliva and blood will be taken. Participants will then undergo a DXA scan to assess body composition and an ultrasound scan on the mid-thigh region of both legs for the assessment of muscle thickness. Maximal leg strength will be determined using Biodex. After the baseline measurements, a knee brace will be placed on one of the legs to start the immobilization period.

Day 1 - 3

During the immobilization period, participants will collect daily saliva samples upon waking.



Day 4

Participants will visit the lab in the fasted state. The knee brace will be removed and subjects will lie on the laboratory bed for the infusion trial. A catheter will be placed in both arms. Before beginning the infusion, a baseline blood sample will be obtained. Following the collection of the baseline blood sample, the first infusion (tracers and 2DG) will be initiated via one of the catheters and continued for the entire duration of the trial. Blood samples will be collected from the other catheter at multiple time points. After 1.5 hours, muscle biopsies are collected under local anesthesia from both legs. Another muscle biopsy will be taken from the immobilized and control leg 2 hours later, signifying the end of the fasted state measurements. Next, to simulate conditions after a meal, the second infusion containing a mixture of amino acids and dextrose will be started. Additional muscle biopsies will be collected from both legs at 90 and 180 minutes of the amino acid/dextrose infusion. The last muscle biopsy marks the end of the infusion trial. After ending the infusion trial, body composition, muscle thickness, muscle cross sectional area, and muscular strength will be measured.