Stefan Keslacy

Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise.

OBJECTIVE Long, uninterrupted bouts of sedentary behavior are thought to negatively influence postprandial glucose and insulin concentrations. We examined the effects of a 1-h bout of morning exercise versus intermittent walking bouts of short duration on glucose excursions and insulin secretion over 12-h. MATERIALS/METHODS Eleven young, obese individuals (18-35 years, BMI>30kg/m(2)) with impaired glucose tolerance were studied on three 12-h study days: 1) sedentary behavior (SED); 2) sedentary behavior with 1-h morning exercise (EX) at 60%-65% VO2peak; and 3) sedentary behavior with 12-hourly, 5-min intervals of exercise (INT) at 60%-65% VO2peak. Meals (1046kJ/meal) were provided every 2-h. Blood samples were collected every 10 min and measured for glucose, insulin, and c-peptide concentrations. RESULTS Glucose iAUC (12-h) was attenuated in the INT and SED conditions compared to the EX condition (P<0.05). Glucose concentrations were higher in the EX compared to the SED condition for ~150min (20% of the study day), and comparison of the EX-INT study days revealed that glucose concentrations were greater for~240min (~1/3 of the 12-hday). In the SED condition, the 12-h insulin iAUC was ~15% higher (P<0.05) compared to the INT and EX conditions. Insulin production rate was found to increase ~20% with INT exercise vs. the SED and EX condition (P<0.05). CONCLUSIONS Short, frequent periods of exercise attenuated glucose excursions and insulin concentrations in obese individuals to a greater degree than an equal amount of exercise performed continuously in the morning.

Gastric bypass up-regulates insulin signaling pathway

OBJECTIVE In the severely obese, Roux-en-Y gastric bypass (RYGB) reverses diabetes before body weight loss occurs. We determined changes in protein expression of insulin receptor (IR), its substrates (IRS1 and IRS2), and their phosphorylated state (p-IR and p-IRS1/2) in skeletal muscle (SM), liver and adipose tissue (AT), and GLUT4 in SM and AT, 14 and 28 d after RYGB to gaining insight into the time-related dynamics of insulin transduction pathway that may contribute to diabetes resolution. BACKGROUND RYGB induces a rapid weight loss followed by a slower weight loss period, leading to reversal of diabetes. We hypothesize that diabetes reversal is due to RYGB-induced up-regulation of insulin signaling pathway. METHODS Diet-induced obese rats had RYGB or sham-operation (obese-controls). Daily food intake, body weight, glucose, insulin, and adiponectin were measured. IR, IRS1, IRS2, p-IR, and p-IRS1/2 were measured in SM, liver, and AT and GLUT4 in SM and AT, 14 and 28 d after RYGB, respectively, reflecting the rapid and slower weight loss periods after RYGB. RESULTS On day 14, in RYGB rats versus obese-controls, food intake, body weight, and fat mass decreased. Rats became normo-glycemic and had low insulin levels and elevated glucose:insulin ratio and decreased adiponectin concentrations. This persisted to day 28, except that adiponectin rose. No change in IR occurred on day 14, in RYGB rats versus obese-controls. By day 28 RYGB rats had a higher IR expression in SM and liver, but no changes in AT. RYGB induced a time-related increase in p-IR in liver and in pIRS1/2 in SM and liver. An increase in GLUT4 occurred by day 28 in SM and AT. CONCLUSIONS Improvement in diabetes occurred after RYGB due to up-regulation in key insulin pathway proteins at several levels, predominantly in SM and liver in association with ongoing caloric restriction, body weight, and fat mass loss.

The Metabolic Costs of Reciprocal Supersets vs. Traditional Resistance Exercise in Young Recreationally Active Adults

Kelleher, AR, Hackney, KJ, Fairchild, TJ, Keslacy, S, and Ploutz-Snyder, LL. The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults. J Strength Cond Res 24(4): 1043-1051, 2010-An acute bout of traditional resistance training (TRAD) increases energy expenditure (EE) both during exercise and in the postexercise period. Reciprocal supersets (SUPERs) are a method of resistance training that alternates multiple sets of high-intensity agonist-antagonist muscle groups with limited recovery. The purpose of this study was to compare the energy cost of SUPERs and TRAD both during and in the postexercise period. We hypothesized that SUPERs would produce greater exercise EE relative to the duration of exercise time and greater excess postexercise oxygen consumption (EPOC) than TRAD of matched work. Ten recreationally active, young men each participated in 2 exercise protocols: SUPER, followed 1 week later by TRAD matched within using a 10-repetition maximum load for 6 exercises, 4 sets, and repetitions. Participants were measured for oxygen consumption and blood lactate concentration during exercise and 60 minutes postexercise after each exercise bout. No significant differences were observed in aerobic exercise EE between trials (SUPER 1,009.99 ± 71.42 kJ; TRAD 954.49 ± 83.31 kJ); however, when expressed relative to time, the exercise EE was significantly greater during SUPER (34.70 ± 2.97 kJ·min−1) than TRAD (26.28 ± 2.43 kJ·min−1). Excess postexercise oxygen consumption was significantly greater after SUPER (79.36 ± 7.49 kJ) over TRAD (59.67 ± 8.37 kJ). Average blood lactate measures were significantly greater during SUPER (5.1 ± 0.9 mmol·L−1) than during TRAD (3.8 ± 0.6 mmol·L−1). Reciprocal supersets produced greater exercise kJ·min−1, blood lactate, and EPOC than did TRAD. Incorporating this method of resistance exercise may benefit exercisers attempting to increase EE and have a fixed exercise volume with limited exercise time available.

Satiety, but not total PYY, is increased with continuous and intermittent exercise

This study determined the hormonal and subjective appetite responses to exercise (1‐h continuous versus intermittent exercise throughout the day) in obese individuals.

Physical Activity Offsets the Negative Effects of a High-Fructose Diet.

OBJECTIVE This study aimed to determine the interaction between a high-fructose diet and PA levels on postprandial lipidemia and inflammation in normal-weight, recreationally active individuals. METHODS Twenty-two men and women (age, 21.2 ± 0.6 yr; body mass index, 22.5 ± 0.6 kg · m(-2)) consumed an additional 75 g of fructose for 14 d on two separate occasions: high physical activity (PA) (approximately 12,500 steps per day) (FR+active) and low PA (approximately 4500 steps per day) (FR+inactive). A fructose-rich test meal was given before and at the end of each intervention. Blood was sampled at baseline and for 6 h after the meal for triglycerides (TG), VLDL, total cholesterol, glucose, insulin, tumor necrosis factor-α, interleukin 6, and C-reactive protein. RESULTS Log-transformed TG area under the curve (AUC) significantly increased from before (10.1 ± 0.1 mg · dL(-1) × min for 6 h) to after (10.3 ± 0.08 mg · dL(-1) × min for 6 h, P = 0.04) the FR+inactive intervention, with an 88% increase in Δ peak TG (P = 0.009) and an 84% increase in Δ peak VLDL (P = 0.002). Δ Peak interleukin 6 also increased by 116% after the FR+inactive intervention (P = 0.009). Insulin total AUC significantly decreased after FR+active intervention (P = 0.04), with no change in AUC after the FR+inactive intervention. No changes were observed in glucose, tumor necrosis factor-α, and C-reactive protein concentrations (P > 0.05). CONCLUSIONS Low PA during a period of high fructose intake augments fructose-induced postprandial lipidemia and inflammation, whereas high PA minimizes these fructose-induced metabolic disturbances. Even within a young healthy population, maintenance of high PA (>12,500 steps per day) decreases susceptibility to cardiovascular risk factors associated with elevated fructose consumption.

Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition

Persons with Down syndrome (DS) exhibit low muscle strength that significantly impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits muscle weakness in vivo and may be a useful model to examine DS-associated muscle dysfunction. Therefore, the purpose of this experiment was to directly assess skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms of DS-associated muscle weakness. Soleus muscles were harvested from anesthetized male Ts65Dn and wild-type (WT) colony controls. In vitro muscle contractile experiments revealed normal force generation of nonfatigued Ts65Dn soleus, but a 12% reduction in force was observed during recovery from fatiguing contractions compared with WT muscle (P < 0.05). Indicators of oxidative stress and mitochondrial oxidative capacity were assessed to reveal potential mechanisms of DS-associated muscle weakness. Protein expression of copper-zinc superoxide dismutase (SOD1), a triplicated gene in persons with DS and Ts65Dn mice, was increased 25% (P < 0.05) in Ts65Dn soleus. Nontriplicated antioxidant protein expression was similar between groups. Lipid peroxidation was unaltered in Ts65Dn animals, but protein oxidation was 20% greater compared with controls (P < 0.05). Cytochrome-c oxidase expression was 22% lower in Ts65Dn muscle (P < 0.05), while expression of citrate synthase was similar between groups. Microarray analysis revealed alteration of numerous pathways in Ts65Dn muscle, including proteolysis, glucose and fat metabolism, neuromuscular transmission, and ATP biosynthesis. In summary, despite biochemical and gene expression differences in soleus muscle of Ts65Dn animals, the functional properties of skeletal muscle likely contribute a minor part to the in vivo muscle weakness.

Role of respiratory system impedance in the difference of ventilatory control between children and adults

How children are able to adapt their ventilation to the intensity of exercise faster than adults remain unclear. We hypothesized that differences of VE observed between children and adults depend on either peripheral chemoreceptors or central command activity. We examined ventilatory control parameters in either normoxic or hypoxic condition (FI 02 =0.15). We analyzed the adaptability of the respiratory exchanges by (i) the measurement of ventilatory kinetics time-constant and (ii) the central command by the mouth-occlusion pressure (P0.1). A group of nine pre-pubescent children (mean age 9.5+/-1 years) and a group of eight adults (mean age 24+/-3.1 years) performed a constant-load exercise. In normoxia, children had significantly shorter time-constant (tau) VCO2 (respectively, 38.5+/-4.3 and 53.1+/-5.3s; P<0.001), tau VE (respectively, 52.5+/-13.1s vs. 66.1+/-12.3s; P<0.001), and tau P0.1 (57.4+/-15.4 and 61.0+/-12.9s, respectively; P<0.001) than adults. In hypoxia, children exhibited shorter tau P0.1/VT/Ti compare to adults. Reinforced by the significant correlation between tau VE and tau P0.1/VT/Ti for children but not adults, we concluded that ventilatory response differences could be due in part to the respiratory system impedance.

Chapter 21:Targeting NF-κB Inflammatory and Prosurvival Signalling in Alzheimer's Disease

Multi-factorial evidence supports the concept that chronic inflammation contributes to the progression of Alzheimers disease. NF-kB is a key component in a major signaling cascade mediating inflammation, but NF-kB activation also supports neuronal survival in certain contexts. An important avenue of drug development lies in understanding the balance between attenuating NF-kB-mediated inflammatory processes that contribute to Alzheimers disease progression while maintaining its closely linked pro-survival signaling. This review discusses evidence supporting a contributory role for NF-kB-mediated inflammation in Alzheimers pathogenesis, and pharmacological strategies that suppress this pathway. Also reviewed is evidence that development of agents that engage the pro-survival/neuroprotective arm of the NF-kB signaling pathway could prove beneficial in Alzheimers disease therapy.