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1.
Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia.
McQueen, G, Lay, A, Lally, J, Gabay, AS, Collier, T, Lythgoe, DJ, Barker, GJ, Stone, JM, McGuire, P, MacCabe, JH, et al
Psychopharmacology. 2020;(2):443-451
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Abstract
RATIONALE There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. OBJECTIVES The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). METHODS In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. RESULTS Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). CONCLUSIONS These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.
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Modified sprint interval training protocols. Part II. Psychological responses.
Townsend, LK, Islam, H, Dunn, E, Eys, M, Robertson-Wilson, J, Hazell, TJ
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2017;(4):347-353
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Abstract
Sprint-interval training (SIT) is a viable method to improve health and fitness. However, researchers have questioned the utility of SIT because of its strenuous nature. The current study aimed to determine if manipulating the sprint and recovery duration, while maintaining the 1:8 work to rest ratio, could uncover a more favourable SIT protocol. Nine healthy active males (age, 23.3 ± 3.0 years; body mass index, 22.4 ± 2.2 kg·m-2; maximal oxygen consumption, 48.9 ± 5.3 mL·kg-1·min-1) participated in 3 experimental running SIT sessions: (i) 30:240 (4 × 30-s efforts, 240-s recovery), (ii) 15:120 (8 × 15-s efforts, 120-s recovery), (iii) 5:40 (24 × 5-s efforts, 40-s recovery), and (iv) a final behavioural choice follow-up session. Affect, intentions, task self-efficacy, enjoyment, and preference were evaluated. Midway through exercise, affect became more positive for 5:40 compared with 30:240 (p < 0.05) and postexercise affect was greater for both 5:40 (p = 0.014) and 15:120 (p = 0.015) compared with 30:240. Participants expressed greater intentions to perform 5:40 3 and 5 times/week compared with 15:120 and 30:240 (p < 0.05). Participants felt more confident in their ability to perform 5:40 (p = 0.001) and 15:120 (p = 0.008) compared with 30:240. The 5:40 session was also rated as more enjoyable than 15:120 (p = 0.025) and 30:240 (p = 0.026). All participants preferred the 5:40 protocol. These data suggest that shorter sprints with more repetitions are perceived as more enjoyable and lead to greater intentions to engage in SIT.
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Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.
Hogenkamp, PS, Zhou, W, Dahlberg, LS, Stark, J, Larsen, AL, Olivo, G, Wiemerslage, L, Larsson, EM, Sundbom, M, Benedict, C, et al
International journal of obesity (2005). 2016;(11):1687-1692
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Abstract
BACKGROUND In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. OBJECTIVE To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). METHODS Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m-2) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m-2), both before and 30 min after consumption of a standardized meal (~260 kcal). RESULTS Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups. CONCLUSION Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.
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Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit.
Areta, JL, Burke, LM, Camera, DM, West, DW, Crawshay, S, Moore, DR, Stellingwerff, T, Phillips, SM, Hawley, JA, Coffey, VG
American journal of physiology. Endocrinology and metabolism. 2014;(8):E989-97
Abstract
The myofibrillar protein synthesis (MPS) response to resistance exercise (REX) and protein ingestion during energy deficit (ED) is unknown. In young men (n = 8) and women (n = 7), we determined protein signaling and resting postabsorptive MPS during energy balance [EB; 45 kcal·kg fat-free mass (FFM)(-1)·day(-1)] and after 5 days of ED (30 kcal·kg FFM(-1)·day(-1)) as well as MPS while in ED after acute REX in the fasted state and with the ingestion of whey protein (15 and 30 g). Postabsorptive rates of MPS were 27% lower in ED than EB (P < 0.001), but REX stimulated MPS to rates equal to EB. Ingestion of 15 and 30 g of protein after REX in ED increased MPS ~16 and ~34% above resting EB (P < 0.02). p70 S6K Thr(389) phosphorylation increased above EB only with combined exercise and protein intake (~2-7 fold, P < 0.05). In conclusion, short-term ED reduces postabsorptive MPS; however, a bout of REX in ED restores MPS to values observed at rest in EB. The ingestion of protein after REX further increases MPS above resting EB in a dose-dependent manner. We conclude that combining REX with increased protein availability after exercise enhances rates of skeletal muscle protein synthesis during short-term ED and could in the long term preserve muscle mass.
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Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.
Catoire, M, Mensink, M, Boekschoten, MV, Hangelbroek, R, Müller, M, Schrauwen, P, Kersten, S
PloS one. 2012;(11):e51066
Abstract
Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max). Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.
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High-Intensity Interval Resistance Training (HIRT) influences resting energy expenditure and respiratory ratio in non-dieting individuals.
Paoli, A, Moro, T, Marcolin, G, Neri, M, Bianco, A, Palma, A, Grimaldi, K
Journal of translational medicine. 2012;:237
Abstract
BACKGROUND The benefits of exercise are well established but one major barrier for many is time. It has been proposed that short period resistance training (RT) could play a role in weight control by increasing resting energy expenditure (REE) but the effects of different kinds of RT has not been widely reported. METHODS We tested the acute effects of high-intensity interval resistance training (HIRT) vs. traditional resistance training (TT) on REE and respiratory ratio (RR) at 22 hours post-exercise. In two separate sessions, seventeen trained males carried out HIRT and TT protocols. The HIRT technique consists of: 6 repetitions, 20 seconds rest, 2/3 repetitions, 20 secs rest, 2/3 repetitions with 2'30″ rest between sets, three exercises for a total of 7 sets. TT consisted of eight exercises of 4 sets of 8-12 repetitions with one/two minutes rest with a total amount of 32 sets. We measured basal REE and RR (TT0 and HIRT0) and 22 hours after the training session (TT22 and HIRT22). RESULTS HIRT showed a greater significant increase (p < 0.001) in REE at 22 hours compared to TT (HIRT22 2362 ± 118 Kcal/d vs TT22 1999 ± 88 Kcal/d). RR at HIRT22 was significantly lower (0.798 ± 0.010) compared to both HIRT0 (0.827 ± 0.006) and TT22 (0.822 ± 0.008). CONCLUSIONS Our data suggest that shorter HIRT sessions may increase REE after exercise to a greater extent than TT and may reduce RR hence improving fat oxidation. The shorter exercise time commitment may help to reduce one major barrier to exercise.
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Gastric emptying after pickle-juice ingestion in rested, euhydrated humans.
Miller, KC, Mack, GW, Knight, KL
Journal of athletic training. 2010;(6):601-8
Abstract
CONTEXT Small volumes of pickle juice (PJ) relieve muscle cramps within 85 seconds of ingestion without significantly affecting plasma variables. This effect may be neurologic rather than metabolic. Understanding PJ's gastric emptying would help to strengthen this theory. OBJECTIVE To compare gastric emptying and plasma variables after PJ and deionized water (DIW) ingestion. DESIGN Crossover study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS Ten men (age = 25.4 ± 0.7 years, height = 177.1 ± 1.6 cm, mass = 78.1 ± 3.6 kg). INTERVENTION(S): Rested, euhydrated, and eunatremic participants ingested 7 mL·kg⁻¹ body mass of PJ or DIW on separate days. MAIN OUTCOME MEASURE(S): Gastric volume was measured at 0, 5, 10, 20, and 30 minutes postingestion (using the phenol red dilution technique). Percentage changes in plasma volume and plasma sodium concentration were measured preingestion (-45 minutes) and at 5, 10, 20, and 30 minutes postingestion. RESULTS Initial gastric volume was 624.5 ± 27.4 mL for PJ and 659.5 ± 43.8 mL for DIW (P > .05). Both fluids began to empty within the first 5 minutes (volume emptied: PJ = 219.2 ± 39.1 mL, DIW = 305.0 ± 40.5 mL, P < .05). Participants who ingested PJ did not empty further after the first 5 minutes (P > .05), whereas in those who ingested DIW, gastric volume decreased to 111.6 ± 39.9 mL by 30 minutes (P < .05). The DIW group emptied faster than the PJ group between 20 and 30 minutes postingestion (P < .05). Within 5 minutes of PJ ingestion, plasma volume decreased 4.8% ± 1.6%, whereas plasma sodium concentration increased 1.6 ± 0.5 mmol·L⁻¹ (P < .05). Similar changes occurred after DIW ingestion. Calculated plasma sodium content was unchanged for both fluids (P > .05). CONCLUSIONS The initial decrease in gastric volume with both fluids is likely attributable to gastric distension. Failure of the PJ group to empty afterward is likely due to PJ's osmolality and acidity. Cardiovascular reflexes resulting from gastric distension are likely responsible for the plasma volume shift and rise in plasma sodium concentration despite nonsignificant changes in plasma sodium content. These data support our theory that PJ does not relieve cramps via a metabolic mechanism.
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Myocardial FFA metabolism during rest and atrial pacing in humans.
Bergman, BC, Tsvetkova, T, Lowes, B, Wolfel, EE
American journal of physiology. Endocrinology and metabolism. 2009;(2):E358-66
Abstract
There is limited in vivo data in humans evaluating myocardial fat utilization during increased heart work. This study was done to determine myocardial free fatty acid (FFA) metabolism during rest and atrial pacing, which increases cardiac work without changing arterial substrate concentration. We studied seven healthy men and women (age = 49.7 +/- 3.9 yr, BMI = 23.4 +/- 1.1 kg/m(2), Vo(2max) = 35.5 +/- 3.0 ml.kg(-1).min(-1), ejection fraction = 68 +/- 3%). After 3 days of dietary control, coronary sinus, femoral arterial and venous, and peripheral venous catheters were placed. Subjects received [(13)C]bicarbonate followed by a continuous infusion of [1-(13)C]palmitate through the end of the study. Arterial and coronary sinus blood sampling and measurements of resting coronary sinus blood flow were made during rest and atrial pacing to 120 beats/min. MVo(2) increased (P < 0.05) from rest to atrial pacing. Coronary sinus FFA concentration was significantly lower than arterial through rest and atrial pacing (P = 0.007). Isotopically measured myocardial palmitate uptake increased significantly from rest to atrial pacing (P = 0.03). Approximately one-third of palmitate delivery was extracted by the myocardium during rest and atrial pacing. Myocardial V(13)CO(2) production and palmitate oxidation increased significantly from rest (P < 0.01) to atrial pacing. Net glycerol balance was significantly greater than zero during rest (P = 0.04) but not different from zero during atrial pacing (P = 0.13). These data suggest that myocardial lipid uptake and oxidation increase with greater heart work during atrial pacing, with a similar relative proportion of fat oxidation to total myocardial energy expenditure.
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Individual responsiveness to exercise-induced fat loss is associated with change in resting substrate utilization.
Barwell, ND, Malkova, D, Leggate, M, Gill, JM
Metabolism: clinical and experimental. 2009;(9):1320-8
Abstract
Fat loss in response to exercise training varies between individuals, even when differences in compliance to the exercise program are accounted for. The purpose of this study was to investigate whether individual variation in change in fasting respiratory quotient (RQ) after exercise training contributes to this interindividual variability. Fifty-five premenopausal women participated in a 7-week endurance-type exercise training program; and fitness, body composition, and resting substrate utilization and metabolic rate in the fasted state were assessed at baseline and postintervention. Total net energy expenditure of the exercise intervention (exEE) was determined from heart rate obtained in all exercise sessions and individualized calibration of the heart rate vs oxygen uptake relationship. Dietary intake and physical activity (by constant heart rate monitoring) were assessed at baseline and during the final week of the intervention. Mean change in fat mass for the group was -0.97 kg (range, +2.1 to -5.3 kg). The strongest correlate of change in fat mass was exEE (r = 0.60, P < .0005). Change in fasting RQ correlated significantly (r = -0.26, P = .05) with the residual for change in fat mass after adjusting for the effects of both exEE and change in energy intake, explaining 7% of the variance. In multiple regression analysis, exEE (P < .0005) and change in fasting RQ (P = .02) were the only statistically significant independent predictors of change in fat mass, together explaining 40.2% of the variance. Thus, fat loss in response to exercise training depends not only on exercise energy expenditure but also on exercise training-induced changes in RQ at rest. This suggests that development of strategies to maximize the change in resting fat oxidation in response to an exercise training program may help individuals to maximize exercise-induced fat loss.
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Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids.
Drummond, MJ, McCarthy, JJ, Fry, CS, Esser, KA, Rasmussen, BB
American journal of physiology. Endocrinology and metabolism. 2008;(6):E1333-40
Abstract
Sarcopenia, skeletal muscle loss during aging, is associated with increased falls, fractures, morbidity, and loss of independence. MicroRNAs (miRNAs) are novel posttranscriptional regulators. The role of miRNAs in cell size regulation after an anabolic stimulus in human skeletal muscle is unknown. We hypothesized that aging would be associated with a differential expression of skeletal muscle primary miRNA (pri-miRNA) and mature miRNA (miR). To test this hypothesis, we used real-time PCR and immunoblotting before and after an anabolic stimulus (resistance exercise + ingestion of a 20-g leucine-enriched essential amino acid solution) to measure the expression of muscle-specific miRNAs (miR-1, miR-133a, and miR-206), upstream regulators (MyoD and myogenin), and downstream targets [insulin-like growth factor-I, histone deacetylase-4, myocyte enhancing factor-2, and Ras homolog enriched in brain (Rheb)] in skeletal muscle of young and older men. Muscle biopsies were obtained at baseline and 3 and 6 h after exercise. At baseline, we found pri-miRNA-1-1, -1-2, -133a-1, and -133a-2 expression elevated in older compared with young men (P < 0.05). Pri-miRNA-1-2, -133a-1, and -133a-2 were reduced at 6 h after exercise only in the young men compared with baseline, whereas pri-miRNA-206 was elevated at different postexercise time points in older and young men (P < 0.05). Compared with baseline, miR-1 was reduced only in the young men, whereas Rheb protein was increased in both age groups after the anabolic stimulus (P < 0.05). We conclude that skeletal muscle primary and mature miRNA expression in young men is readily altered by an anabolic stimulus of resistance exercise + essential amino acid ingestion. However, aging is associated with higher basal skeletal muscle primary miRNA expression and a dysregulated miRNA response after the anabolic stimulus.