Gretchen A. Casazza

Evaluation of exercise and training on muscle lipid metabolism

To evaluate the hypothesis that endurance training increases intramuscular triglyceride (IMTG) oxidation, we studied leg net free fatty acid (FFA) and glycerol exchange during 1 h of cycle ergometry at two intensities before training [45 and 65% of peak rate of oxygen consumption (V˙o 2 peak)] and after training [65% pretrainingV˙o 2 peak, same absolute workload (ABT), and 65% posttrainingV˙o 2 peak, same relative intensity (RLT)]. Nine male subjects (178.1 ± 2.5 cm, 81.8 ± 3.3 kg, 27.4 ± 2.0 yr) were tested before and after 9 wk of cycle ergometer training, five times per week at 75%V˙o 2 peak. The power output that elicited 66.1 ± 1.1% ofV˙o 2 peak before training elicited 54.0 ± 1.7% after training due to a 14.6 ± 3.1% increase inV˙o 2 peak. Training significantly ( P < 0.05) decreased pulmonary respiratory exchange ratio (RER) values at ABT (0.96 ± 0.01 at 65% pre- vs. 0.93 ± 0.01 posttraining) but not RLT (0.95 ± 0.01). After training, leg respiratory quotient (RQ) was not significantly different at either ABT (0.98 ± 0.02 pre- vs. 0.98 ± 0.03 posttraining) or RLT (1.01 ± 0.02). Net FFA uptake was increased at RLT but not ABT after training. FFA fractional extraction was not significantly different after training or at any exercise intensity. Net glycerol release, and therefore IMTG lipolysis calculated from three times net glycerol release, did not change from rest to exercise or at ABT but decreased at the same RLT after training. Muscle biopsies revealed minor muscle triglyceride changes during exercise. Simultaneous measurements of leg RQ, net FFA uptake, and glycerol release by working legs indicated no change in leg FFA oxidation, FFA uptake, or IMTG lipolysis during leg cycling exercise that elicits 65% pre- and 54% posttrainingV˙o 2 peak. Training increases working muscle FFA uptake at 65%V˙o 2 peak, but high RER and RQ values at all work intensities indicate that FFA and IMTG are of secondary importance as fuels in moderate and greater-intensity exercise.

Effects of exercise intensity and training on lipid metabolism in young women

We examined the effects of exercise intensity and training [12 wk, 5 days/wk, 1 h, 75% peak oxygen consumption (V˙o 2 peak)] on lipolysis and plasma free fatty acid (FFA) flux in women ( n = 8; 24.3 ± 1.6 yr). Two pretraining trials (45 and 65% ofV˙o 2 peak) and two posttraining trials [same absolute workload (65% of oldV˙o 2 peak; ABT) and same relative workload (65% of newV˙o 2 peak; RLT)] were performed using infusions of [1,1,2,3,3-2H]glycerol and [1-13C]palmitate. Pretraining rates of FFA appearance (Ra), disappearance (Rd), and oxidation (Rox p) were similar between the 65% (6.8 ± 0.6, 6.2 ± 0.7, 3.1 ± 0.3 μmol ⋅ kg-1 ⋅ min-1, respectively) and the 45% ofV˙o 2 peaktrials. At ABT and RLT training increased FFA Ra to 8.4 ± 1.0 and 9.7 ± 1.1 μmol ⋅ kg-1 ⋅ min-1, Rd to 8.3 ± 1.0 and 9.5 ± 1.1 μmol ⋅ kg-1 ⋅ min-1, and Rox p to 4.8 ± 0.4 and 6.7 ± 0.7 μmol ⋅ kg-1 ⋅ min-1, respectively ( P ≤ 0.05). Total FFA oxidation from respiratory exchange ratio was also elevated after training at ABT and RLT, with all of the increase attributed to plasma FFA sources. Pretraining, glycerol Ra was higher during exercise at 65 than 45% of V˙o 2 peak(6.9 ± 0.9 vs. 4.7 ± 0.6 μmol ⋅ kg-1 ⋅ min-1) but was not changed by training. In young women 1) plasma FFA kinetics and oxidation are not linearly related to exercise intensity before training, 2) training increases FFA Ra, Rd, and Rox p whether measured at given absolute or relative exercise intensities, 3) whole body lipolysis (glycerol Ra) during exercise is not significantly impacted by training, and 4) training-induced increases in plasma FFA oxidation are the main contributor to elevated total FFA oxidation during exercise exertion after training.

Muscle net glucose uptake and glucose kinetics after endurance training in men.

We evaluated the hypotheses that alterations in glucose disposal rate (Rd) due to endurance training are the result of changed net glucose uptake by active muscle and that blood glucose is shunted to working muscle during exercise requiring high relative power output. We studied leg net glucose uptake during 1 h of cycle ergometry at two intensities before training [45 and 65% of peak rate of oxygen consumption (V˙o 2 peak)] and after training [65% pretrainingV˙o 2 peak, same absolute workload (ABT), and 65% posttrainingV˙o 2 peak, same relative workload (RLT)]. Nine male subjects (178.1 ± 2.5 cm, 81.8 ± 3.3 kg, 27.4 ± 2.0 yr) were tested before and after 9 wk of cycle ergometer training, five times a week at 75%V˙o 2 peak. The power output that elicited 66.0 ± 1.1% ofV˙o 2 peak before training elicited 54.0 ± 1.7% after training. Whole body glucose Rd decreased posttraining at ABT (5.45 ± 0.31 mg ⋅ kg-1 ⋅ min-1at 65% pretraining to 4.36 ± 0.44 mg ⋅ kg-1 ⋅ min-1) but not at RLT (5.94 ± 0.47 mg ⋅ kg-1 ⋅ min-1). Net glucose uptake was attenuated posttraining at ABT (1.87 ± 0.42 mmol/min at 65% pretraining and 0.54 ± 0.33 mmol/min) but not at RLT (2.25 ± 0.81 mmol/min). The decrease in leg net glucose uptake at ABT was of similar magnitude as the drop in glucose Rd and thus could explain dampened glucose flux after training. Glycogen degradation also decreased posttraining at ABT but not RLT. Leg net glucose uptake accounted for 61% of blood glucose flux before training and 81% after training at the same relative (65%V˙o 2 peak) workload and only 38% after training at ABT. We conclude that 1) alterations in active muscle glucose uptake with training determine changes in whole body glucose kinetics; 2) muscle glucose uptake decreases for a given, moderate intensity task after training; and 3) hard exercise (65%V˙o 2 peak) promotes a glucose shunt from inactive tissues to active muscle.

Can changes in body mass and total body water accurately predict hyponatremia after a 161-km running race?

Objective:To relate changes in body mass, total body water (TBW), extracellular fluid (ECF), and serum sodium concentration ([Na+]) from a 161-km ultramarathon to finish time and incidence of hyponatremia. Design:Observational. Setting:The 2008 Rio Del Lago 100-Mile (161-km) Endurance Run in Granite Bay, California. Participants:Forty-five runners. Main Outcome Measurements:Pre-race and post-race body mass, TBW, ECF, and serum [Na+]. Results:Body mass and serum [Na+] significantly decreased 2% to 3% (P < 0.001) from pre-race to post-race, but TBW and ECF were unchanged. Significant relationships were observed between finish time and percentage change in body mass (r = 0.36; P = 0.01), TBW (r = 0.50; P = 0.007), and ECF (r = 0.61; P = 0.003). No associations were found between post-race serum [Na+] and percentage change in body mass (r = −0.04; P = 0.94) or finish time (r = 0.5; P = 0.77). Hyponatremia (serum [Na+] < 135 mmol/L) was present among 51.2% of finishers. Logistic regression prediction equation including pre-race TBW and percentage changes in TBW and ECF had an 87.5% concordance with the classification of hyponatremia. Conclusions:Hyponatremia occurred in over half of the 161-km ultramarathon finishers but was not predicted by change in body mass. The combination of pre-race TBW and percentage changes in TBW and ECF explained 87.5% of the variation in the incidence of hyponatremia. Clinical Significance:Exercise-associated hyponatremia can occur simultaneously with dehydration and cannot be predicted by weight checks at races.

Body composition of 161-km ultramarathoners.

This study compares body composition characteristics with performance among participants in a 161-km trail ultramarathon. Height, mass, and percent body fat from bioimpedance spectroscopy were measured on 72 starters (17 women, 55 men). Correlation analyses were used to compare body characteristics with finish time, and unpaired t-tests were used to compare characteristics of finishers with non-finishers. Mean (+/-SD) BMI (kg x m(-2)) was 24.8+/-2.7 (range 19.1-32.2) for the men and 21.2+/-2.1 (range 18.1-26.7) for the women. Among the three fastest runners, BMI values ranged from 22.1 to 23.4 for men and 21.5 to 22.9 for women. Mean (+/-SD) percent body fat values for men and women were 17+/-5 (range 5-35) and 21+/-6 (range 10-29) , and ranged from 6 to 14 and 14 to 27 among the fastest three men and women. There was a significant positive correlation (r(2)=0.23; p=0.0025) between percent body fat and finish time for men but not for women, and percent body fat values were lower for finishers than non-finishers for men (p=0.03) and women (p=0.04). We conclude that despite wide variations in BMI and percent body fat among ultramarathon participants, the faster men have lower percent body fat values than the slower men, and finishers have lower percent body fat values than non-finishers.

Vigorous exercise increases brain lactate and Glx (glutamate + glutamine): A dynamic 1H-MRS study

Vigorous exercise increases lactate and glucose uptake by the brain in excess of the increase in brain oxygen uptake. The metabolic fate of this non-oxidized carbohydrate entering the brain is poorly understood, but accumulation of lactate in the brain and/or increased net synthesis of amino acid neurotransmitters are possible explanations. Previous proton magnetic resonance spectroscopy (1H-MRS) studies using conventional pulse sequences have not detected changes in brain lactate following exercise. This contrasts with 1H-MRS studies showing increased brain lactate when blood lactate levels are raised by an intravenous infusion of sodium lactate. Using a J-editing 1H-MRS technique for measuring lactate, we demonstrated a significant 19% increase in lactate in the visual cortex following graded exercise to approximately 85% of predicted maximum heart rate. However, the magnitude of the increase was insufficient to account for more than a small fraction of the non-oxidized carbohydrate entering the brain with exercise. We also report a significant 18% increase in Glx (combined signal from glutamate and glutamine) in visual cortex following exercise, which may represent an activity-dependent increase in glutamate. Future studies will be necessary to test the hypothesis that non-oxidized carbohydrate entering the brain during vigorous exercise is directed, in part, toward increased net synthesis of amino acid neurotransmitters. The possible relevance of these findings to panic disorder and major depression is discussed.

Improved Metabolic Health Alters Host Metabolism in Parallel with Changes in Systemic Xeno-Metabolites of Gut Origin

Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight) were identified before and after a 14–17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1) Changes in plasma xeno-metabolites (“non-self” metabolites of dietary or gut microbial origin) following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid]) or in the overnight-fasted state (e.g., lower γ-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT α-ketoglutaric acid (α-KG), fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary “signatures” of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the hosts metabolome.

Acute Modulation of Cortical Glutamate and GABA Content by Physical Activity.

Converging evidence demonstrates that physical activity evokes a brain state characterized by distinctive changes in brain metabolism and cortical function. Human studies have shown that physical activity leads to a generalized increase in electroencephalography power across regions and frequencies, and a global increase in brain nonoxidative metabolism of carbohydrate substrates. This nonoxidative consumption of carbohydrate has been hypothesized to include increased de novo synthesis of amino acid neurotransmitters, especially glutamate and GABA. Here, we conducted a series of proton magnetic resonance spectroscopy studies in human volunteers before and after vigorous exercise (≥80% of predicted maximal heart rate). Results showed that the resonance signals of both glutamate and GABA increased significantly in the visual cortex following exercise. We further demonstrated a similar increase in glutamate following exercise in an executive region, the anterior cingulate cortex. The increase in glutamate was similar when using echo times of 30 and 144 ms, indicating that exercise-related T2 relaxation effects across this range of relaxation times did not account for the findings. In addition, we found preliminary evidence that more physical activity during the preceding week predicts higher resting glutamate levels. Overall, the results are consistent with an exercise-induced expansion of the cortical pools of glutamate and GABA, and add to a growing understanding of the distinctive brain state associated with physical activity. A more complete understanding of this brain state may reveal important insights into mechanisms underlying the beneficial effects of physical exercise in neuropsychiatric disorders, neurorehabilitation, aging, and cognition. SIGNIFICANCE STATEMENT Increasing evidence suggests that distinctly different brain states are associated with sedentary behavior compared with physically active behavior. Metabolic studies show that the nonoxidative consumption of carbohydrates by the brain increases greatly during vigorous activity. Prior studies have suggested that one component of this metabolic shift may involve increasing the reserves of neurotransmitters in the brain via de novo synthesis from carbohydrate substrates. The current study reports the results of three experiments that support this hypothesis by showing increased cortical content of glutamate and GABA following physical activity. Understanding how brain metabolism and function differ during sedentary versus active behavioral states may provide important insights into the neurotherapeutic potential of exercise.

Catecholamines and Obesity: Effects of Exercise and Training

Excess body fat in obese individuals can affect the catecholamine response to various stimuli. Indeed, several studies report lower plasma catecholamine concentrations in obese subjects compared with nonobese subjects in response to submaximal or maximal exercise. This low catecholamine response reflects decreased sympathetic nervous system (SNS) activity. Although the relationship between the SNS and obesity is not well established, some authors have suggested that low SNS activity may contribute to the development of obesity. A decreased catecholamine response could affect α- and β-adrenoceptor sensitivity in adipose tissue, reducing lipolysis and increasing fat stores. Few studies have examined the effects of obesity on the plasma catecholamine response at rest and during exercise in adolescents. It is interesting to note that the effects of age, sex, and degree of obesity and the impact of very intense exercise on the catecholamine response have not yet been well examined. Moreover, the hormonal concentrations measured in the majority of obesity studies did not take into account plasma volume changes. This methodological factor can also undoubtedly influence plasma catecholamine results.

Whole-Body Cryostimulation Limits Overreaching in Elite Synchronized Swimmers

INTRODUCTION Elite athletes frequently undergo periods of intensified training (IT) within their normal training program. These periods can lead athletes into functional overreaching, characterized by high perceived fatigue, impaired sleep, and performance. Because whole-body cryostimulation (WBC) has been proven to be an effective recovery method in the short term (<76 h), we investigated whether daily WBC sessions during IT could prevent exercise and sleep-related signs of overreaching. METHODS After a normal training week (BASE), 10 elite synchronized swimmers performed two 2-wk IT periods in a randomized crossover fashion using WBC daily (ITWBC) or not (ITCON), separated by 9 d of light training. Swim time trials (400 m) were performed at BASE and after each IT to quantify blood lactate ([La]B), HR (HR400), salivary alpha amylase ([α-amylase]s400), and cortisol ([cortisol]s400) responses. Swimmers wore a wrist actigraph nightly to monitor sleep patterns. RESULTS Swim speed (400 m), [La]B400, and [α-amylase]s400 decreased from BASE to ITCON, although no significant changes were found after ITWBC. Decreased swim speed was correlated to decreased HR400 and [cortisol]s400. During ITCON, significant decreases in actual sleep duration (-21 ± 7 min) and sleep efficiency (-1.9% ± 0.8%) were observed, with increased sleep latency (+11 ± 5 min) and fatigue compared with BASE, although these variables did not change during ITWBC. Using a qualitative statistical analysis, we observed that daily WBC use resulted in a 98%, 59%, 66%, and 78% chance of preserving these respective variables compared with ITCON. CONCLUSION WBC use during IT helped mitigate the signs of functional overreaching observed during ITCON, such as reduced sleep quantity, increased fatigue, and impaired exercise capacity. These results support the daily use of WBC by athletes seeking to avoid functional overreaching during key periods of competition preparation.