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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

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
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PURPOSE: Lean hypertension (HTN) is characterized by a mechanistically different HTN when compared to obese HTN. The purpose of this study is to assess whether body phenotype influences blood pressure (BP) responses following both acute and chronic exercise. METHODS: Obese (body mass index (BMI) > 30 kg/m2) and

PURPOSE: Lean hypertension (HTN) is characterized by a mechanistically different HTN when compared to obese HTN. The purpose of this study is to assess whether body phenotype influences blood pressure (BP) responses following both acute and chronic exercise. METHODS: Obese (body mass index (BMI) > 30 kg/m2) and lean (BMI < 25 kg/m2) men with pre-hypertension (PHTN) (systolic BP (SBP) 120 - 139 or diastolic BP (DBP) 80 - 89 mm Hg) were asked to participate in a two-phase trial. Phase 1 assessed differences in post-exercise hypotension between groups in response to an acute exercise bout. Phase 2 consisted of a two-week aerobic exercise intervention at 65-70% of heart rate (HR) max on a cycle ergometer. Primary outcome measures were: brachial BP, central (aortic) BP, cardiac output (CO), and systemic vascular resistance (SVR) measured acutely after one exercise session and following two weeks of training. RESULTS: There were no differences between groups for baseline resting brachial BP, central BP, age, or VO2 peak (all P > 0.05). At rest, obese PHTN had greater CO compared to lean PHTN (6.3 ± 1 vs 4.7 ± 1 L/min-1, P = 0.005) and decreased SVR compared to lean PHTN (1218 ± 263 vs 1606 ± 444 Dyn.s/cm5, P = 0.003). Average 60-minute post-exercise brachial and central SBP reduced by 3 mm Hg in Lean PHTN in response to acute exercise (P < 0.005), while significantly increasing 4 mm Hg for brachial and 3 mm Hg for central SBP (P < 0.05). SVR had a significantly greater reduction following acute exercise in lean PHTN (-223 Dyn·s/cm5) compared to obese PHTN (-75 Dyn·s/cm5, P < 0.001). In lean subjects chronic training reduced brachial BP by 4 mm Hg and central BP by 3 mm Hg but training had no effect on the BP’s in obese subjects. Resting BP reduction in response to training was accompanied by reductions in SVR within lean (-169 Dyn·s/cm5, P < 0.001), while obese experienced increased SVR following training (47 Dyn·s/cm5, P < 0.001). CONCLUSION: Hemodynamic response to both acute and chronic exercise training differ between obese and lean individuals.
ContributorsZeigler, Zachary (Author) / Swan, Pamela (Thesis advisor) / Gaesser, Glenn (Committee member) / Buman, Matthew (Committee member) / Angadi, Siddhartha (Committee member) / Farouk, Mookadam (Committee member) / Arizona State University (Publisher)
Created2016