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- All Subjects: Biology
- Creators: Arizona State University
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
Groundwater contamination is of environmental and human health concern. Bioremediation is a nature-based method for contaminant treatment. Bioremediation, which relies on the ability of microorganisms to destroy or transform contaminants, must be reliable and cost-competitive in comparison to more traditional treatment methods. Two hurdles must be overcome to enhance bioremediation’s effectiveness and competitiveness: i) being able to degrade recalcitrant compounds, and ii) being able to control the growth rate and location of microorganisms involved in bioremediation in the subsurface. My dissertation adds foundational knowledge and engineering application on how to biodegrade recalcitrant emerging and legacy halogenated compounds. Generating biotransformation knowledge on the recalcitrant emerging contaminants called per- and polyfluoroalkyl substances (PFAS) may lead to solutions for protecting both people and the planet. In my dissertation, I analyzed PFAS biotransformation and microbial defluorination literature via meta-analytical and bibliometric methods to identify unexplored topics and experimental conditions. The metanalytical work identified trends in PFAS microbial biotransformation science to inform future experimental design.
The second hurdle which must be overcome is being able to control bacterial growth in the subsurface. During bioremediation implementation microbial overgrowth may clog injection wells and the subsurface, leading to reduced porosity and treatment efficacy. Contaminant treatment schemes based on aerobic cometabolism frequently exhibit overgrowth at subsurface injection points for O2 (the electron acceptor) and a labile hydrocarbon (e.g., propane). My dissertation work experimentally evaluated acetylene as a microbial inhibitor for use in controlling microbial overgrowth during trichloroethene (TCE) aerobic cometabolism. I demonstrated that acetylene reduces the likelihood of microbial overgrowth of TCE-degrading microorganisms in soil-free microcosms and aquifer soil columns while retaining TCE degradation capacity. Cumulatively, my dissertation provides foundational knowledge for academics and bioremediation practitioners to develop robust and reliable bioremediation technologies.
ContributorsSkinner, Justin Paul (Author) / Delgado, Anca G. (Thesis advisor) / Rittmann, Bruce E (Committee member) / Chu, Min Ying Jacob (Committee member) / Arizona State University (Publisher)
Created2023