Matching Items (2)
Filtering by
- All Subjects: Syncytin-1
- Creators: Dickinson, Jared
- Creators: Skotak, Nathaniel James
- Member of: Theses and Dissertations
Description
Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular fusion protein syncytin-1. This led to the hypothesis that syncytin-1 could be decreased in the muscle of obese/insulin resistant individuals. In contrast, it was found that obese/insulin resistant subjects had higher syncytin-1 expression in the muscle compared to that of the lean subjects. Across the subjects, syncytin-1 correlated significantly with body mass index, percent body fat, blood glucose and HbA1c levels, insulin sensitivity and muscle protein fractional synthesis rate. The concentrations of specific plasma fatty acids, such as the saturated fatty acid (palmitate) and monounsaturated fatty acid (oleate) are known to be altered in obese/insulin resistant humans, and also to influence the protein synthesis in muscle. Therefore, it was evaluated that the effects of palmitate and oleate on syncytin-1 expression, as well as 4E-BP1 phosphorylation, a key mechanism regulating muscle protein synthesis in insulin stimulated C2C12 myotubes. The results showed that treatment with 20 nM insulin, 300 µM oleate, 300 µM oleate +20 nM insulin and 300 µM palmitate + 300 µM oleate elevated 4E-BP1 phosphorylation. At the same time, 20 nM insulin, 300 µM palmitate, 300 µM oleate + 20 nM insulin and 300 µM palmitate + 300 µM oleate elevated syncytin-1 expression. Insulin stimulated muscle syncytin-1 expression and 4E-BP1 phosphorylation, and this effect was comparable to that observed in the presence of oleate alone. However, the presence of palmitate + oleate diminished the stimulatory effect of insulin on muscle syncytin-1 expression and 4E-BP1 phosphorylation. These findings indicate oleate but not palmitate increased total 4E-BP1 phosphorylation regardless of insulin and the presence of palmitate in insulin mediated C2C12 cells. The presence of palmitate inhibited the upregulation of total 4EB-P1 phosphorylation. Palmitate but not oleate increased syncytin-1 expression in insulin mediated C2C12 myotubes. It is possible that chronic hyperinsulinemia in obesity and/or elevated levels of fatty acids such as palmitate in plasma could have contributed to syncytin-1 overexpression and decreased muscle protein fractional synthesis rate in obese/insulin resistant human muscle.
ContributorsRavichandran, Jayachandran (Author) / Katsanos, Christos (Thesis advisor) / Coletta, Dawn (Committee member) / Dickinson, Jared (Committee member) / Arizona State University (Publisher)
Created2017
Description
This purpose of this study was to develop reliable methods for ultrasound measurements of skeletal muscle architecture, and to identify which specific quadriceps measurements most closely relate to peak isometric torque of the leg extensors. These data were obtained as part of a larger research study and consist of 9 total subjects (4 males, 5 females; age (30.6 ± 13.6yr). Ultrasound images for muscle thickness and pennation angle were obtained for each subject during two separate testing days (separated by 5-10 days). Images were acquired at various anatomical sites of the quadriceps and each image was analyzed using Image J software. Quadriceps muscles assessed for muscle thickness and pennation angle included the vastus lateralis (VL), and vastus intermedius (VI), while rectus femoris (RF) was assessed only for muscle thickness. Peak isometric torque measurements were obtained at 60 degrees of knee angle for knee extension using an isokinetic dynamometer. Results show that the methods chosen for ultrasound measurement produced reliable inter-day results for muscle thickness and pennation angle. VL muscle thickness and pennation angle obtained at the lateral site corresponding to 39% of leg length was highly related to peak isometric torque for knee extension. The results of this study identify specific measurement sites that are related to muscle function. In addition, these data further validate that ultrasound measurement is reliable to measure muscle thickness and pennation angle in skeletal muscle.
ContributorsSkotak, Nathaniel James (Author) / Dickinson, Jared (Thesis director) / Vidt, Meghan (Committee member) / Luden, Nick (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05