Regulation of Muscle Protein Phenotype in Humans With Obesity

Regulation of Muscle Protein Phenotype in Humans With Obesity

A hallmark of muscle changes in obesity is an altered muscle fiber type profile, characterized by a reduced proportion of Type I fibers - a shift associated with adverse obesity-related health outcomes. This alteration can be linked to changes in the expression of myosin heavy chain (MHC) protein isoforms in the skeletal muscle of individuals with obesity. The investigators aim to modulate the metabolism of muscle MHC isoforms to uncover the biological mechanisms underlying this disrupted expression pattern in muscle of humans with obesity.

Humans with obesity have typically lower proportion of Type I muscle fibers in skeletal muscle. These fiber types, known for their high capacity for glucose uptake, have also greater sensitivity to fuel metabolism compared with Type II fibers, even within the adverse metabolic environment of obesity. Altered expression of skeletal muscle myosin heavy chain (MHC) protein isoforms, molecular marker of fiber types, may explain this shift.

This project aims to uncover the biological mechanisms sustaining disrupted MHC protein metabolism in the skeletal muscle of individuals with obesity. The investigators will compare overall protein metabolism between humans with obesity and lean controls, with a specific focus on MHC isoforms. They will assess MHC isoform gene expression, associated molecular regulators, and synthesis rates of the MHC isoforms involved in muscle fiber programming. Acute aerobic exercise and elevated plasma amino acids will be used as experimental tools to target transcriptional and translational processes related to MHC gene expression. The findings are expected to reveal mechanisms responsible for the unfavorable fiber type profile observed in the skeletal muscle of humans with obesity.

Inclusion Criteria:

• ability to sign informed consent form
• body mass index (BMI), 18-26 kg/m2 (lean subjects), 32-50 kg/m2 (subjects with obesity)

Exclusion Criteria:

• prescription or over-the-counter medication
• supplements known to affect protein metabolism (i.e., amino acids, protein, omega-3 fatty acids)
• diabetes
• acute illness
• liver disease
• uncontrolled metabolic disease, including renal disease
• heart disease related to atrial fibrillation, history of syncope, limiting or unstable angina, congestive heart failure or ECG documented abnormalities
• low hemoglobin or hematocrit
• use of anabolic steroids or corticosteroids (within 3 months)
• not classified as inactive/sedentary based on the Stanford Brief Activity Survey and accelerometry data
• participation in a weight-loss regimen
• extreme dietary practices (i.e., vegan, vegetarian)
• smoking
• pregnancy
• gastro-intestinal surgery
• any other condition or event considered exclusionary by the PI and the study physician.