Full metadata
Title
Effect of fatty acids and insulin on syncytin-1 and 4E-BP1 in skeletal muscle
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.
Date Created
2017
Contributors
- Ravichandran, Jayachandran (Author)
- Katsanos, Christos (Thesis advisor)
- Coletta, Dawn (Committee member)
- Dickinson, Jared (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
vii, 50 pages : illustrations (some color)
Language
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.I.46358
Statement of Responsibility
by Jayachandran Ravichandran
Description Source
Retrieved on June 13, 2018
Level of coding
full
Note
Partial requirement for: M.S., Arizona State University, 2017
Note type
thesis
Includes bibliographical references (pages 43-47)
Note type
bibliography
Field of study: Biology
System Created
- 2018-02-01 07:13:27
System Modified
- 2021-08-26 09:47:01
- 2 years 8 months ago
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