Date of Completion
energy deficit, testosterone, dietary protein, ACL reconstruction, disuse atrophy
Dr. Nancy Rodriguez
Dr. Christopher Blesso
Dr. Stefan Pasiakos
Field of Study
Doctor of Philosophy
Skeletal muscle atrophy occurs with disuse after musculoskeletal injury, and during periods of sustained energy deficit. Manipulating dietary protein intake or supplementing with testosterone under muscle wasting conditions may protect muscle mass and/or function by increasing muscle protein synthesis, attenuating muscle protein breakdown, and enhancing myogenesis either directly or via upstream modulation of inflammatory signaling. The protective effect of dietary protein was evaluated in Study 1. Vastus lateralis muscle collected perioperatively from anterior cruciate ligament (ACL) reconstruction patients assigned to an optimal (OP: 2.0 g·kg-1·d-1, n =3) or adequate (AP: 1.0 g·kg-1·d-1, n =2) protein diet for two weeks prior to surgery was analyzed for intracellular markers of myogenesis, inflammation, and protein turnover. Thigh circumference and strength were measured before surgery and 2, 4, and 8 weeks postoperatively. Testosterone-mediated intracellular signaling regulating muscle mass was determined in Study 2 before and after a 28-day, severe diet- and exercise-induced energy deficit with weekly supplementation of 200 mg of testosterone enanthate (TEST; n=10) or a placebo (PLA; n=10) at baseline, 60 minutes after a bout of cycle ergometry, and 6 hours post-exercise. A protein-containing meal was consumed following the second biopsy.
Higher protein intake before surgery did not influence perioperative markers of inflammation, myogenesis, or protein synthesis. Gene expression of the proteolytic marker muscle ring finger 1 (MuRF1) was greater in AP versus OP individuals at the time of surgery. Postoperative thigh circumference at week 2, 4, and 8 relative to baseline was associated with perioperative gene expression of paired box 7 (Pax7), fibroblast growth factor-inducible 14 (Fn14), and tumor necrosis factor-α-receptor (TNFα-R), respectively. Similarly, perioperative markers of inflammation and myogenesis were associated with quadriceps strength at 8 weeks post-surgery relative to pre-surgery measures. Testosterone supplementation during energy deficit attenuated Fn14 gene expression and increased androgen receptor protein content at baseline, and upregulated expression of the myogenic regulatory factor MyoD and attenuated proteolytic gene expression after exercise and feeding.
In total, findings from Study 1 and Study 2 indicate integration of intramuscular inflammation, dietary protein intake, and testosterone-mediated intracellular signaling in the regulation of muscle mass during conditions of muscle wasting.
Howard, Emily E., "Integrated Role of Intramuscular Inflammation, Dietary Protein, and Testosterone Supplementation in the Regulation of Skeletal Muscle Mass during Muscle Wasting Conditions" (2019). Doctoral Dissertations. 2338.