Nicholas P. Greene

Comparative efficacy of water and land treadmill training for overweight or obese adults.

PURPOSE No known previous research has been published to explore the efficacy of underwater treadmill (UTM) exercise training for the obese. Thus, the purpose of this study was to compare changes in physical fitness, body weight, and body composition in physically inactive, overweight, and obese adults after 12 wks of land treadmill (LTM) or UTM training. METHODS Fifty-seven physically inactive, overweight, and obese men (n = 25) and women (n = 32) participated in this investigation. The mean +/- SEM age, weight, body mass index (BMI), and V O2max upon entry were 44 +/- 2 yr, 90.5 +/- 2.4 kg, 30.5 +/- 0.7 kg.m, and 27.1 +/- 0.7 mL O2.kg.min, respectively. Subjects were randomly assigned to exercise three times per week for 12 wk on either LTM (n = 29) or UTM (n = 28) matched for intensity and volume. Session volume was progressively increased from 250 to 500 kcal per session by week 6 and remained at 500 kcal through week 12. Before and after training, V O2max was assessed by the Bruce treadmill protocol with open-circuit calorimetry, and body composition was assessed by dual-energy ray absorptiometry. Data were analyzed by a 2 (training) x 2 (exercise mode) x 2 (gender) ANOVA repeated across training (alpha = 0.05). RESULTS Training responses were not different between genders. After either UTM or LTM training, V O2max was significantly increased (+3.6 +/- 0.4 mL O2.kg.min), whereas body weight (-1.2 +/- 0.3 kg), BMI (-0.56 +/- 0.11 kg.m), body fat percentage (-1.3% +/- 1.3%), and fat mass (-1.1 +/- 0.3 kg) were significantly reduced (pooled means for UTM and LTM). Regional leg lean body mass (LBM) was significantly increased with both CTM and UTM (0.4 +/- 0.3 and 0.8 +/- 0.2 kg, respectively). An increase in total LBM approached significance with UTM training only (+0.6 +/- 0.3 kg, P = 0.0599). CONCLUSIONS UTM and LTM training are equally capable of improving aerobic fitness and body composition in physically inactive overweight individuals, but UTM training may induce increases in LBM.

Insulin resistance syndrome blunts the mitochondrial anabolic response following resistance exercise

Metabolic risk factors associated with insulin resistance syndrome may attenuate augmentations in skeletal muscle protein anabolism following contractile activity. The purpose of this study was to investigate whether or not the anabolic response, as defined by an increase in cumulative fractional protein synthesis rates (24-h FSR) following resistance exercise (RE), is blunted in skeletal muscle of a well-established rodent model of insulin resistance syndrome. Four-month-old lean (Fa/?) and obese (fa/fa) Zucker rats engaged in four lower body RE sessions over 8 days, with the last bout occurring 16 h prior to muscle harvest. A priming dose of deuterium oxide ((2)H(2)O) and (2)H(2)O-enriched drinking water were administered 24 h prior to euthanization for assessment of cumulative FSR. Fractional synthesis rates of mixed (-5%), mitochondrial (-1%), and cytosolic (+15%), but not myofibrillar, proteins (-16%, P = 0.012) were normal or elevated in gastrocnemius muscle of unexercised obese rats. No statistical differences were found in the anabolic response of cytosolic and myofibrillar subfractions between phenotypes, but obese rats were not able to augment 24-h FSR of mitochondria to the same extent as lean rats following RE (+14% vs. +28%, respectively). We conclude that the mature obese Zucker rat exhibits a mild, myofibrillar-specific suppression in basal FSR and a blunted mitochondrial response to contractile activity in mixed gastrocnemius muscle. These findings underscore the importance of assessing synthesis rates of specific myocellular subfractions to fully elucidate perturbations in basal protein turnover rates and differential adaptations to exercise stimuli in metabolic disease.

Diet-induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration

Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors (MRFs) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice.

Mitochondrial quality control, promoted by PGC‐1α, is dysregulated by Western diet‐induced obesity and partially restored by moderate physical activity in mice

Skeletal muscle mitochondrial degeneration is a hallmark of insulin resistance/obesity marked by lost function, enhanced ROS emission, and altered morphology which may be ameliorated by physical activity (PA). However, no prior report has examined mitochondrial quality control regulation throughout biogenesis, fusion/fission dynamics, autophagy, and mitochondrial permeability transition pore (MPTP) in obesity. Therefore, we determined how each process is impacted by Western diet (WD)‐induced obesity and whether voluntary PA may alleviate derangements in mitochondrial quality control mechanisms. Despite greater mitochondrial content following WD (COX‐IV and Cytochrome C), induction of biogenesis controllers appears impaired (failed induction of PGC‐1α). Mitochondrial fusion seems diminished (reduced MFN2, Opa1 proteins), with no significant changes in fission, suggesting a shift in balance of dynamics regulation favoring fission. Autophagy flux was promoted in WD (reduced p62, increased LC3II:I ratio); however, mitophagy marker BNIP3 is reduced in WD which may indicate reduced mitophagy despite enhanced total autophagy flux. MPTP regulator Ant mRNA is reduced by WD. Few processes were impacted by physical activity. Finally, mitochondrial quality control processes are partially promoted by PGC‐1α, as PGC‐1α transgenic mice display elevated mitochondrial biogenesis and autophagy flux. Additionally, these mice exhibit elevated Mfn1 and Opa1 mRNA, with no change in protein content suggesting these factors are transcriptionally promoted by PGC‐1α overexpression. These data demonstrate dysfunctions across mitochondrial quality control in obesity and that PGC‐1α is sufficient to promote multiple, but not necessarily all, aspects of mitochondrial quality control. Mitochondrial quality control may therefore be an opportune target to therapeutically treat metabolic disease.

Translational machinery of mitochondrial mRNA is promoted by physical activity in Western diet-induced obese mice.

Mitochondria‐encoded proteins are necessary for oxidative phosphorylation; however, no report has examined how physical activity (PA) and obesity affect mitochondrial mRNA translation machinery. Our purpose was to determine whether Western diet (WD)‐induced obesity and voluntary wheel running (VWR) impact mitochondrial mRNA translation machinery and whether expression of this machinery is dictated by oxidative phenotype.

Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice

Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity. Eight-week-old C57BL/6J mice were fed a Western diet (WD) or normal chow (NC, control) for 4 weeks; afterwards, groups were divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks. WD-SED animals had a median histology score of 2, whereas WD-VWR was not different from NC groups (median score 1). There was no difference in mRNA of inflammatory markers Il6 and Tnfa in WD animals. WD animals had 50% lower mitochondrial content (COX IV and Cytochrome C proteins), 50% lower Pgc1a mRNA content, and reduced content of mitochondrial fusion and fission markers. Markers of autophagy were increased in VWR animals, regardless of obesity, as measured by 50% greater LC3-II/I ratio and 40% lower p62 protein content. BNIP3 protein content was 30% less in WD animals compared with NC animals, regardless of physical activity. Diet-induced obesity results in derangements in mitochondrial quality control that appear to occur prior to the onset of hepatic inflammation. Moderate physical activity appears to enhance basal autophagy in the liver; increased autophagy may provide protection from hepatic fat accumulation.

Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice

Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20–40% of cancer‐related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia. Therefore, our purpose was to determine if mitochondrial degeneration precedes cancer‐induced muscle wasting in tumour‐bearing mice.

Aquatic Treadmill Training Reduces Blood Pressure Reactivity to Physical Stress

PURPOSE Endurance exercise may reduce blood pressure and improve vasodilatory capacity, thereby blunting the hypertensive response to stress. Therefore, we sought to test the efficacy of a novel model of low-impact endurance training, the aquatic treadmill (ATM), to improve blood pressure (BP) parameters. METHODS Sixty sedentary adults were randomized to 12-wk of either ATM (n = 36 [19 males and 17 females], 41 ± 2 yr, 173.58 ± 1.58 cm, 93.19 ± 3.15 kg) or land-based treadmill (LTM, n = 24 [11 males, 13 females], 42 ± 2 yr, 170.39 ± 1.94 cm, 88.14 ± 3.6 kg) training, three sessions per week, progressing to 500 kcal per session, 85% VO2max. The maximal Bruce treadmill test protocol was performed before and after training with BP measured before, at the end of each stage, and for 5 min after exercise testing. Twelve subjects (five ATM and seven LTM) volunteered for biopsies of the vastus lateralis before and after training, and muscle samples were assessed for endothelial nitric oxide synthase content. Data collected during exercise testing were analyzed using group by training ANCOVA repeated across training, α = 0.05. RESULTS ATM but not LTM training significantly reduced resting diastolic BP (-3.2 mm Hg), exercise systolic BP (range 9-18.2 mm Hg lower for each exercise stage), diastolic BP (3.2-8.1 mm Hg), mean arterial pressure (4.8-8.3 mm Hg, lower than LTM posttraining), and pulse pressure (7.5-15 mm Hg) during stages of exercise stress and recovery (P < 0.05). In addition, an increase (+31%) in skeletal muscle endothelial nitric oxide synthase content after training (P < 0.05) occurred in only the ATM group. Body mass (-1.27 kg) and VO2max (+3.6 mL · kg(-1) · min(-1)) changes were significant for both groups (P < 0.001). CONCLUSION ATM training can reduce BP reactivity to physical stress.

Anabolic responses to acute and chronic resistance exercise are enhanced when combined with aquatic treadmill exercise

Aquatic treadmill (ATM) running may simultaneously promote aerobic fitness and enhance muscle growth when combined with resistance training (RT) compared with land-treadmill (LTM) running. Therefore, we examined acute and chronic physiological responses to RT, concurrent RT-LTM, and concurrent RT-ATM. Forty-seven untrained volunteers (men: n = 23, 37 ± 11 yr, 29.6 ± 4.6 kg/m(2); women: n = 24, 38 ± 12 yr, 27.53 ± 6.4 kg/m(2)) from the general population were tested for V̇o2max, body composition, and strength before and after training. All groups performed 12 wk of RT (2 wk, 3 × 8-12 sets at 60 to approximately 80% 1-repetition maximum). The RT-LTM and RT-ATM groups also performed 12 wk of LTM or ATM training (2 wk immediately post-RT and 1 wk in isolation, 60-85% V̇o2max, 250-500 kcal/session). Additionally, 25 subjects volunteered for muscle biopsy prior to and 24 h post-acute exercise before and after training. Stable isotope labeling (70% (2)H2O, 3 ml/kg) was utilized to quantify 24 h post-exercise myofibrillar fractional synthesis rates (myoFSR). Mixed-model ANOVA revealed that RT-ATM but not RT-LTM training produced greater chronic increases in lean mass than RT alone (P < 0.05). RT-LTM training was found to elicit the greatest decreases in percent body fat (-2.79%, P < 0.05). In the untrained state, acute RT-ATM exercise elicited higher 24-h myoFSRs compared with RT (+5.68%/day, P < 0.01) and RT-LTM (+4.08%/day, P < 0.05). Concurrent RT-ATM exercise and training elicit greater skeletal muscle anabolism than RT alone or RT-LTM.

Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size

Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia.