PGC1α

PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α  −1 nucleosome (−1N) position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP) expressed lower levels of NTPGC1α than those with the −1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and −1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133

Determinants of the changes in glycemic control with exercise training in type 2 diabetes:A randomized trial

To assess the determinants of exercise training-induced improvements in glucose control (HbA1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).Changes in HbA1C were associated with changes in adiponectin (r = -0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = -0.26; P<0.03), and PGC-1α (r = -0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA1C.Decreases in HbA1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.ClinicalTrials.gov NCT00458133

Exercise-induced changes in central adiposity during a RCT: effect of exercise dose and associations with compensation

Context: Exercise can decrease central adiposity, but the effect of exercise dose and the relationship between central adiposity and exercise-induced compensation is unclear. Objective: Test the effect of exercise dose on central adiposity change and the association between central adiposity and exercise-induced weight compensation. Methods: In this ancillary analysis of a 6-month randomized controlled trial, 170 participants with overweight or obesity (mean±SD BMI: 31.5±4.7 kg/m2) were randomized to a control group or exercise groups that reflected exercise recommendations for health (8 kcal/kg/week [KKW]) or weight loss and weight maintenance (20 KKW). Waist circumference was measured, and dual-energy X-ray absorptiometry assessed central adiposity. Predicted weight change was estimated and weight compensation (weight change minus predicted weight change) was calculated. Results: Between-group change in waist circumference (control: 0.0 cm [95% CI: -1.0,1.0], 8 KKW: -0.7 cm [95% CI: -1.7,0.4], 20 KKW: -1.3 cm [95% CI: -2.4, -0.2]) and visceral adipose tissue (VAT; control: -0.02 kg [95% CI: -0.07,0.04], 8 KKW: -0.01 kg [95% CI: -0.07,0.04], 20 KKW: -0.04 kg [95% CI: -0.10,0.02]) was similar (P≥0.23). Most exercisers (82.6%) compensated (predicted weight change lower than actual weight change). Exercisers who compensated exhibited a 2.5 cm (95% CI: 0.8,4.2) and 0.23 kg (95% CI: 0.14,0.31) increase in waist circumference and VAT, respectively, versus those who did not (P&lt;0.01). Desire to eat predicted VAT change during exercise (β=0.21; P=0.03). Conclusions: In the presence of significant weight compensation, exercise at doses recommended for health and weight loss and weight maintenance leads to negligible changes in central adiposity

Precision exercise medicine: understanding exercise response variability

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability. In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability531811411153The consensus meeting that led to the writing of this manuscript was held with the financial support of the Pennington Biomedical Research Foundation, the Pennington Biomedical Research Center Division of Education, the LSU Boyd Professorship and the John W. Barton, Sr. Chair in Genetics and Nutrition. No funding and/or honorarium was provided to any member of the writing group for the production of this manuscrip

The Effect of Exercise Training Modality on Serum Brain Derived Neurotrophic Factor Levels in Individuals with Type 2 Diabetes

Introduction: Brain derived neurotrophic factor (BDNF) has been implicated in memory, learning, and neurodegenerative disease. However, the relationship of BDNF with cardiometabolic risk factors is unclear, and the effect of exercise training on BDNF has not been previously explored in individuals with type 2 diabetes. Methods: Men and women (N=150) with type 2 diabetes were randomized to an aerobic exercise (aerobic), resistance exercise (resistance), or a combination of both (combination) for 9 months. Serum BDNF levels were evaluated at baseline and follow-up from archived blood samples. Results: Baseline serum BDNF was not associated with fitness, body composition, anthropometry, glucose control, or strength measures (all, p\u3e0.05). Similarly, no significant change in serum BDNF levels was observed following exercise training in the aerobic (-1649.4 pg/ml, CI: -4768.9 to 1470.2), resistance (-2351.2 pg/ml, CI: -5290.7 to 588.3), or combination groups (-827.4 pg/ml, CI: -3533.3 to 1878.5) compared to the control group (-2320.0 pg/ml, CI: -5750.8 to 1110.8). However, reductions in waist circumference were directly associated with changes in serum BDNF following training (r=0.25, p=0.005). Conclusions: Serum BDF was not associated with fitness, body composition, anthropometry, glucose control, or strength measures at baseline. Likewise, serum BDNF measures were not altered by 9 months of aerobic, resistance, or combination training. However, reductions in waist circumference were associated with decreased serum BDNF levels. Future studies should investigate the relevance of BDNF with measures of cognitive function specifically in individuals with type-2 diabetes

Neonatal head and torso vibration exposure during inter-hospital transfer

Inter-hospital transport of premature infants is increasingly common, given the centralisation of neonatal intensive care. However, it is known to be associated with anomalously increased morbidity, most notably brain injury, and with increased mortality from multifactorial causes. Surprisingly, there have been relatively few previous studies investigating the levels of mechanical shock and vibration hazard present during this vehicular transport pathway. Using a custom inertial datalogger, and analysis software, we quantify vibration and linear head acceleration. Mounting multiple inertial sensing units on the forehead and torso of neonatal patients and a preterm manikin, and on the chassis of transport incubators over the duration of inter-site transfers, we find that the resonant frequency of the mattress and harness system currently used to secure neonates inside incubators is ~9Hz. This couples to vehicle chassis vibration, increasing vibration exposure to the neonate. The vibration exposure per journey (A(8) using the ISO 2631 standard) was at least 20% of the action point value of current European Union regulations over all 12 neonatal transports studied, reaching 70% in two cases. Direct injury risk from linear head acceleration (HIC15) was negligible. Although the overall hazard was similar, vibration isolation differed substantially between sponge and air mattresses, with a manikin. Using a Global Positioning System datalogger alongside inertial sensors, vibration increased with vehicle speed only above 60 km/h. These preliminary findings suggest there is scope to engineer better systems for transferring sick infants, thus potentially improving their outcomes

Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a reduction in muscle quality. However, there is inadequate empirical evidence to determine whether changes in muscle quality following exercise are associated with improvement in cardiorespiratory fitness (CRF) in individuals with T2DM. The objective of this study was to investigate the association between change in muscle quality following a 9-month intervention of aerobic training (AT), resistance training (RT) or a combination of both (ATRT) and cardiorespiratory fitness (CRF) in individuals with T2DM. Material and Methods A total of 196 participants were randomly assigned to a control, AT, RT, or combined ATRT for a 9-months intervention. The exposure variable was change in muscle quality [(Post: leg muscle strength/leg muscle mass)-[(Pre: leg muscle strength/leg muscle mass)]. Dependent variables were change in CRF measures including absolute and relative VO2peak, and treadmill time to exhaustion (TTE) and estimated metabolic equivalent task (METs). Results Continuous change in muscle quality was independently associated with change in absolute (β = 0.015; p = 0.019) and relative (β = 0.200; p = 0.005) VO2peak, and TTE (β = 0.170; p = 0.043), but not with estimated METs (p > 0.05). A significant trend was observed across tertiles of change in muscle quality for changes in absolute (β = 0.050; p = 0.005) and relative (β = 0.624; p = 0.002) VO2peak following 9 months of exercise training. No such association was observed for change in TTE and estimated METs (p > 0.05). Discussion: The results from this ancillary study suggest that change in muscle quality following exercise training is associated with a greater improvement in CRF in individuals with T2DM. Given the effect RT has on increasing muscle quality, especially as part of a recommended training program (ATRT), individuals with T2DM should incorporate RT into their AT regimens to optimize CRF improvement

Acute effects of brisk walking on sugary snack cravings in overweight people, affect and responses to a manipulated stress situation and to a sugary snack cue: a crossover study.

Research has shown that acute exercise reduces urges for chocolate in normal weight people. This study aimed to examine the effects of an acute exercise bout on urges to consume sugary snacks, affect as well as 'psychological and physiological responses' to stress and a 'sugary snack cue', in overweight individuals. Following 3 days of chocolate-abstinence, 47 overweight, sugary snack consumers were assessed, in 2 randomly ordered conditions, in a within-subject design: 15-min brisk walk or passive control. Following each, participants completed 2 tasks: Stroop color-word interference task, and handling sugary snacks. Urges for sugary snacks, affective activation and valence were assessed. ANOVAs revealed significant condition x time interaction effects for: urges to consume sugary snacks, affective valence and activation. Obtained data show that exercise reduces urges for sugary snacks and attenuates urges in response to the stress situation and the cue in overweight people

Validation of the Activity Preference Assessment: a tool for quantifying children’s implicit preferences for sedentary and physical activities

Background High levels of sedentary behavior and low physical activity are associated with poor health, and the cognitive determinants of these behaviors in children and adolescents are not well understood. To address this gap, we developed a novel, non-verbal, computer-based assessment to quantify the degree to which youth prefer to be sedentary relative to physically active in their leisure time. Methods The Activity Preference Assessment (APA) uses a forced-choice paradigm to understand implicit decision-making processes when presented with common sedentary and physical activities. The APA bias score ranges from − 100 to + 100, with positive scores indicating a relative preference for sedentary activities, and negative scores representing a preference for physical activities. In 60 children ages 8–17 years, we assessed the validity of this behavioral task against a free-choice play observation, accelerometry-measured activity, anthropometrics and body composition, and cardiorespiratory fitness. We explored neighborhood, family, and individual-level factors that may influence implicit activity preferences. Test-retest reliability was assessed over one week. Results The majority of children (67%) preferred sedentary relative to physical activities. APA bias scores were positively associated with sedentary time during free-choice play. In girls, bias scores were negatively associated with average daily MVPA. APA bias scores were positively associated with body fat and negatively associated with cardiorespiratory fitness. These findings were independent of age, sex, and race/ethnicity. Neighborhood access to physical activity spaces, the number of people in the home, perceived physical self-competence (e.g., coordination, strength), and self-reported depressive symptoms were associated with activity preferences. The intra-class correlation for test-retest reliability was r = 0.59. Conclusions The APA shows promise as a novel tool for quantifying children’s relative preference for sedentary versus physical activities. Implicit bias scores from the APA are clinically meaningful, as shown by significant associations with adiposity and cardiorespiratory fitness. Future longitudinal studies should examine the directionality of the association between preferences and health markers, and the degree to which implicit activity preferences are modifiable. Importantly, the task only takes an average of 10 min to complete, highlighting a potential role as an efficient screening tool for the propensity to be sedentary versus physically active