Regulation of Muscle Protein Phenotype in Humans With Obesity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Whole-Muscle Protein Synthesis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •ability to sign informed consent form
- •body mass index (BMI), 18-26 kg/m2 (lean subjects), 32-50 kg/m2 (subjects with obesity)
排除标准
- •prescription or over-the-counter medication
- •supplements known to affect protein metabolism (i.e., amino acids, protein, omega-3 fatty acids)
- •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)
- •pregnancy
- •gastro-intestinal surgery
- •any other condition or event considered exclusionary by the PI and the study physician.
结局指标
主要结局
Whole-Muscle Protein Synthesis
时间窗: 9 Hours
Protein synthesis rates in whole muscle were quantified as the fractional synthesis rate (FSR), expressed as %/hour - representing the percentage of the entire muscle protein pool newly synthesized per hour. Protein synthesis rates were determined by continuous infusion of a stable isotope-labeled amino acid tracer, followed by measurement of tracer incorporation into the muscle proteins over time. Changes in FSR from baseline were evaluated in response to combined exercise and amino acid infusion.
Synthesis Rates of the Three Myosin Heavy Chain Isoforms (MHC I, MHC IIa, and MHC IIx)
时间窗: 9 Hours
Synthesis rates of the myosin heavy chain protein isoforms were quantified as the fractional synthesis rate (FSR), expressed as %/hour - representing the percentage of each of the three myosin heavy chain isoform protein pool newly synthesized per hour. Protein synthesis rates were determined by continuous infusion of a stable isotope-labeled amino acid tracer, followed by measurement of tracer incorporation into each of the three myosin heavy chain isoform protein Changes in FSR from baseline were evaluated in response to combined exercise and amino acid infusion.
Messenger RNA (mRNA) Expression of Three Myosin Heavy Chain Isoforms (MHC I, MHC IIa, and MHC IIx)
时间窗: 9 Hours
Messenger RNA (mRNA) expressions of the myosin heavy chain isoforms were determined by measuring the abundance of the three specific transcripts of the myosin heavy chain isoforms. mRNA was measured using quantitative reverse transcription PCR (qRT-PCR). Changes in mRNA expression from baseline were evaluated in response to combined exercise and amino acid infusion.
次要结局
未报告次要终点
研究者
Lori R. Roust
Principal Investigator
Mayo Clinic