Campos Cristian, Flores-Opazo Marcelo, Valladares-Ide Denisse, Cabello-Verrugio Claudio, Parada Pilar, Morales Francisco, Arredondo Joseline, Peñailillo Luis
Exercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, School of Physical Therapy, Universidad Andres Bello, Santiago, Chile.
Long Active Life Laboratory, Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.
Sci Rep. 2025 Jul 4;15(1):23839. doi: 10.1038/s41598-025-09169-7.
This study aimed to compare the protein content of pathways related to mTORC1 signaling and oxidative metabolism in whole skeletal muscle and isolated muscle fibers from healthy individuals (HEALTHY) and individuals with obesity (OBESE). Muscle biopsies were obtained from 18 individuals. Samples were freeze-dried, and fibers were isolated and fiber-typed for type I and IIa myosin heavy chain isoforms. The protein content of Akt-1, mTOR, p70s6K, S6 ribosomal protein (S6RP), ERK1/2, p38, total protein ubiquitination (TPU), and OXPHOS proteins in whole muscle and isolated fibers was determined using immunoblotting. Muscle fiber morphology was also assessed. Fiber type proportion was similar in HEALTHY, while OBESE showed a greater proportion of type IIa fibers. Fiber cross-sectional area (CSA) was similar in HEALTHY, while OBESE showed greater CSA of type I fibers. Protein content of p70s6K was lower (73%, p = 0.008), while ERK1/2 (29%, p = 0.05) and TPU (32%, p = 0.03) were increased in whole muscle from OBESE compared with HEALTHY. Fiber-specific differences were found in p38 (IIa > I, p = 0.03) in HEALTHY, while OBESE showed different complex II and V (I > IIa, p = 0.03 and p = 0.04, respectively) between fibers. Furthermore, a negative correlation was found between body mass and p70s6K protein content. Our findings suggest that obesity impairs the mTORC1-related protein pathway while increasing degradation in individuals with obesity.
本研究旨在比较健康个体（HEALTHY）和肥胖个体（OBESE）的全骨骼肌以及分离的肌纤维中与mTORC1信号传导和氧化代谢相关途径的蛋白质含量。从18名个体获取肌肉活检样本。样本经冷冻干燥处理，分离出肌纤维并根据I型和IIa型肌球蛋白重链亚型进行纤维分型。使用免疫印迹法测定全肌肉和分离纤维中Akt-1、mTOR、p70s6K、S6核糖体蛋白（S6RP）、ERK1/2、p38、总蛋白泛素化（TPU）以及氧化磷酸化蛋白的含量。同时评估肌纤维形态。HEALTHY组的纤维类型比例相似，而OBESE组中IIa型纤维的比例更高。HEALTHY组的纤维横截面积（CSA）相似，而OBESE组中I型纤维的CSA更大。与HEALTHY组相比，OBESE组全肌肉中p70s6K的蛋白质含量较低（7３%，p = 0.008），而ERK1/２（29%，p = 0.05）和TPU（32%，p = 0.03）有所增加。在HEALTHY组中，p38存在纤维特异性差异（IIa＞I，p = 0.03），而OBESE组的纤维之间，复合物II和V存在差异（I＞IIa，分别为p = 0.03和p = 0.04）。此外，发现体重与p70s6K蛋白质含量之间存在负相关。我们的研究结果表明，肥胖会损害肥胖个体中与mTORC1相关的蛋白质途径，同时增加蛋白质降解。
