Common variants of the resistance mechanism in the Smith Machine: analysis of mechanical loading characteristics and application to strength-oriented and hypertrophy-oriented training

The Smith machine is a pervasive weight-training apparatus, used extensively by a wide population of weight trainers, from novices to high-level athletes. The advantages of using a Smith machine over free-weight resistance are disputed, with conflicting findings reported in the literature. In this study, we are interested in practical differences between 3 types of loading mechanisms found in modern Smith machines. In addition to the basic design comprising a constrained weighted barbell, alterations with a counterweight and a viscous resistance component are examined. The approach taken is that of employing a recently proposed representation of force characteristics that may be exhibited by a trainee and a predictive model of thus effected adaptation. A computer simulation is used to predict the effects of the 3 linear Smith machine designs in the framework of different exercise protocols. Our results demonstrate that each resistance component, vertically constrained load, counterweight, and viscous, can be matched with a particular training context, in which it should be preferred. Thus, a number of practical guidelines for weight-training practitioners are recommended. In summary, (a) at low intensities (55–75% of 1 repetition maximum [1RM]) used in strength-endurance training, a viscous resistance containing the Smith machine was found to offer advantages over both a constrained load only and counterweighted designs; (b) at medium intensities (75–85% of 1RM) typically employed in hypertrophy-specific training, the counterweighted Smith machine design was found to offer the best choice in terms of high-force development and total external work performed; finally, (c) at high training intensity (90–100% of 1RM), the optimal prescription was found to be more dependent on the specific athlete’s weaknesses, highlighting the need for continual monitoring of the athlete’s force production capabilities. To ensure that appropriate adjustments are made to the athlete’s training regimen, the practitioner should consider the full set of findings of this article and the accompanying discussion.

Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race

Background. We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Methods. Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low N glom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. Results. IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. Conclusions. While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Hypertrophy in the cervical muscles and thoracic discs in bed rest?

The impact of prolonged bed rest on the cervical and upper thoracic spine is unknown. In the 2nd Berlin BedRest Study (BBR2-2), 24 male subjects underwent 60-day bed rest and performed either no exercise, resistive exercise, or resistive exercise with whole body vibration. Subjects were followed for 2 yr after bed rest. On axial cervical magnetic resonance images from the skull to T3, the volumes of the semispinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, middle and posterior scalenes, and anterior scalenes were measured. Disc height, anteroposterior width, and volume were measured from C2/3 to T6/7 on sagittal images. The volume of all muscles, with the exception of semispinalis capitis, increased during bed rest (P < 0.025). There were no significant differences between the groups for changes in the muscles. Increased upper and midthoracic spine disc height and volume (P < 0.001) was seen during bed rest, and disc height increases persisted at least 6 mo after bed rest. Increases in thoracic disc height were greater (P = 0.003) in the resistive vibration exercise group than in control. On radiological review, two subjects showed new injuries to the mid-lower thoracic spine. One of these subjects reported a midthoracic pain incident during maximal strength testing before bed rest and the other after countermeasure exercise on day 3 of bed rest. We conclude that bed rest is associated with increased disc size in the thoracic region and increases in muscle volume at the neck. The exercise device needs to be modified to ensure that load is distributed in a more physiological fashion.

Telomere dynamics during aging in polygenic left ventricular hypertrophy.

Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR), and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2-days), leading to left ventricular hypertrophy (LVH) (13-weeks) and subsequently progression to heart failure (38-weeks). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared to the control strain at 2-days and 38-weeks, but shorter at 13-weeks. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13- or 38-weeks. Tert mRNA and Terc RNA were over-expressed at 38-weeks, while miR-34a was over-expressed at 13-weeks but down-regulated at 38-weeks. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer foetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13-weeks, they were not present at the progression to heart failure at 38-weeks.

Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22

BACKGROUND: Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR).

METHODS AND RESULTS: To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHR × NHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P < 0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r = -0.16, P = 0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F = 10.35, P < 0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy.

CONCLUSION: Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.

Exercise and skeletal muscle gene expression

1. Skeletal muscle is a complex and heterogenous tissue capable of remarkable adaptation in response to exercise training. The role of gene transcription, as an initial target to control protein synthesis, is poorly understood.
2. Mature myofibres contain several hundred nuclei, all of which maintain transcriptional competency, although the localized responsiveness of nuclei is not well known. Myofibres are capable of hypertrophy. These processes require the activation and myogenic differentiation of mononuclear satellite cells that fuse with the enlarging or repairing myofibre.
3. A single bout of exercise in human subjects is capable of activating the expression of many diverse groups of genes.
4. The impact of repeated exercise bouts, typical of exercise training, on gene expression has yet to receive systematic investigation.
5. The molecular programme elicited by resistance exercise and endurance exercise differs markedly. Muscular hypertrophy following resistance exercise is dependent on the activation of satellite cells and their subsequent myogenic maturation. Endurance exercise requires the simultaneous activation of mitochondrial and nuclear genes to enable mitochondrial biogenesis.
6. Future analysis of the regulation of genes by exercise may combine high-throughput technologies, such as gene-chips, enabling the rapid detection and analysis of changes in the expression of many thousands of genes.

Decreased expression of adipogenic genes in obese subjects with type 2 diabetes

Objective: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance.

Research Methods and Procedures: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [ CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARitalic gamma coactivator 1alpha, PPARitalic gamma coactivator 1beta, and PPARdelta] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity.

Results: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 plusminus 1.9 vs. 7.5 plusminus 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 plusminus 0.26 vs. 0.78 plusminus 0.17 mum; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARitalic gamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07).

Discussion: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.

STAT3 signaling is activated in human skeletal muscle following acute resistance exercise

The transcription factor signal transducer and activator of transcription 3 (STAT3) has been identified as a mediator of cytokine signaling and implicated in hypertrophy; however, the importance of this pathway following resistance exercise in human skeletal muscle has not been investigated. In the present study, the phosphorylation and nuclear localization of STAT3, together with STAT3-regulated genes, were measured in the early recovery period following intense resistance exercise. Muscle biopsy samples from healthy subjects (7 males, 23.0 + 0.9 yr) were harvested before and again at 2, 4, and 24 h into recovery following a single bout of maximal leg extension exercise (3 sets, 12 repetitions). Rapid and transient activation of phosphorylated (tyrosine 705) STAT3 was observed at 2 h postexercise. STAT3 phosphorylation paralleled the transient localization of STAT3 to the nucleus, which also peaked at 2 h postexercise. Downstream transcriptional events regulated by STAT3 activation peaked at 2 h postexercise, including early responsive genes c-FOS (800-fold), JUNB (38-fold), and c-MYC (140-fold) at 2 h postexercise. A delayed peak in VEGF (4-fold) was measured 4 h postexercise. Finally, genes associated with modulating STAT3 signaling were also increased following exercise, including the negative regulator SOCS3 (60-fold). Thus, following a single bout of intense resistance exercise, a rapid phosphorylation and nuclear translocation of STAT3 are evident in human skeletal muscle. These data suggest that STAT3 signaling is an important common element and may contribute to the remodeling and adaptation of skeletal muscle following resistance exercise.

Influence of preexercise muscle glycogen content on transcrptional activity of metabolic and myogenic genes in well-trained humans

To determine whether preexercise muscle glycogen content influences the transcription of several early-response genes involved in the regulation of muscle growth, seven male strength-trained subjects performed one-legged cycling exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared with the leg with normal muscle glycogen (Norm) and then the following day completed a unilateral bout of resistance training (RT). Muscle biopsies from both legs were taken at rest, immediately after RT, and after 3 h of recovery. Resting glycogen content was higher in the control leg (Norm leg) than in the Low leg (435 ± 87 vs. 193 ± 29 mmol/kg dry wt; P < 0.01). RT decreased glycogen content in both legs (P < 0.05), but postexercise values remained significantly higher in the Norm than the Low leg (312 ± 129 vs. 102 ± 34 mmol/kg dry wt; P < 0.01). GLUT4 (3-fold; P < 0.01) and glycogenin mRNA abundance (2.5-fold; not significant) were elevated at rest in the Norm leg, but such differences were abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher in the Norm compared with the Low leg [atrogin: 14-fold, P < 0.01; RING (really interesting novel gene) finger: 3-fold, P < 0.05] but decreased for atrogin in Norm following RT (P < 0.05). There were no differences in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm compared with the Low leg. Our results demonstrate that 1) low muscle glycogen content has variable effects on the basal transcription of select metabolic and myogenic genes at rest, and 2) any differences in basal transcription are completely abolished after a single bout of heavy resistance training. We conclude that commencing resistance exercise with low muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy.

Angiotensin converting enzyme inhibition from birth reduces body weight and body fat in Sprague-Dawley rats

In vitro studies have demonstrated that angiotensin II (ANG II) induces adipocyte hyperplasia and hypertrophy. The aim of the present study was to determine the effect of angiotensin-converting enzyme inhibition on body weight, adiposity and blood pressure in Sprague–Dawley rats. From birth half of the animals (n = 15) were given water to drink, while the remainder were administered perindopril in their drinking water (2 mg/kg/day). Food intake, water intake and body weight were measured weekly. Blood pressure was measured by tail cuff plethysmography at 11-weeks. Body fat content and distribution were assessed using dual energy X-ray absorptiometry and Magnetic Resonance Imaging at 12 weeks. Animals administered with perindopril had a body fat proportion that was half that of controls. This was consistent with, but disproportionately greater than the observed differences in food intake and body weight. Perindopril treatment completely removed hypertension. We conclude that the chronic inhibition of ANG II synthesis from birth specifically reduces the development of adiposity in the rat.

Effects of Salvia miltiorrhiza after acute myocardial infarction in rats

Acute myocardial infarction (M!) is the commonest cause of death in the developed countries, and it is on the rise in developing countries. Ramipril is a well-knownAngiotensin-converting enzyme (ACE) inhibitorwhich inhibits conversion ofinactive angiotensin I to active angiotensin II. Experimental studies have shown thatACE inhibitors administered chronicallybefore acuteMImight limitmyocardial infarct size, improve cardiac function and prevent cardiac hypertrophy [1, 2]. The Chinese herb, Salvia miltiorrhiza (SM), has been widely and successfully usedmainly for anginapectoris,MI and stroke [3]. Compared to ramipril, however, there is very limited biochemical information availableto demonstrate themechanismsofSMs
cardio-protective effects. This study thus investigates the possible
biochemical and molecularmechanisms ofsuch effects ofSMin Wistar rats in comparison with those oframipril.

Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3β/4E-BP1, and muscle atrophy, including TNFα/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 ± 0.2 years) and 16 older (70 ± 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40–45% in the type II muscle fibers. TNFα and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3β were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNFα, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.

Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice

Background: It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases.

Objective: We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses.

Methods: C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge.

Results: Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective.

Conclusion: Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Functional and metabolic remodelling in GLUT4-deficient hearts confers hyper-responsiveness to substrate intervention

Impaired glucose uptake is associated with both cardiac hypertrophy and contractile dysfunction, but whether there are common underlying  mechanisms linking these conditions is yet to be determined. Using a ‘gene dose’ Cre-Lox GLUT4-deficient murine model, we examined the effect of suppressed glucose availability on global myocardial gene expression and glycolysis substrate bypass on the function of isolated perfused hearts. Performance of hearts from 22- to 60-week-old male GLUT4 knockout (KO, > 95% reduction in GLUT4), GLUT4 knockdown (KD, 85% reduction in cardiac GLUT4) and C57Bl/6 wild-type (WT) controls was measured ex vivo in Langendorff mode perfusion. DNA microarray was used to profile mRNA expression differences between GLUT4-KO and GLUT4-KD hearts. At 22 weeks, GLUT4-KO hearts exhibited cardiac hypertrophy and impaired contractile function ex vivo, characterized by a 40% decrease in developed pressure. At 60 weeks, dysfunction was accentuated in GLUT4-KO hearts and evident in GLUT4-KD hearts. Exogenous pyruvate (5 mM) restored systolic pressure to a level equivalent to WT (GLUT4-KO, 176.8 ± 13.2 mmHg vs. WT, 146.4 ± 9.56 mmHg) in 22-week-old GLUT4-KO hearts but not in 60-week-old GLUT4-KO hearts. In GLUT4-KO, DNA microarray analysis detected downregulation of a number of genes centrally involved in mitochondrial oxidation and upregulation of other genes indicative of a shift to cytosolic β-oxidation of long chain fatty acids. A direct link between cardiomyocyte GLUT4 deficiency, hypertrophy and contractile dysfunction is demonstrated. These data provide mechanistic insight into the myocardial metabolic adaptations associated with short and long-term insulin resistance and indicate a window of opportunity for substrate intervention and functional ‘rescue’.

The effect of estrogen on Akt signalling and protein synthesis in C2C12 mouse skeletal myotubes

The maintenance of skeletal muscle mass is a critical component of health in both chronic wasting diseases and aging. A considerable amount of progress has been made in the understanding of the signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Akt is seen as a key molecular protein involved in the maintenance of skeletal muscle mass as it has the dual ability to positively influence protein syntheses and negatively regulate protein degradation in its active state (Glass, 2003). Potential mechanisms which may assist with maintaining skeletal muscle mass are the estrogen hormones. Estrogens increase the proliferation of mouse and rat myoblasts and can also attenuate immobilization-induced skeletal muscle atrophy in rats in vivo (Kahlert et al., 1997). No studies have investigated the effect of estrogens on the activation of skeletal muscle hypertrophy and atrophy signalling pathways. Estrogens may contribute to maintaining skeletal muscle mass via their activation of the Akt signalling pathways. Therefore, the aims of the present study were to determine if treatment of C2C12 myotubes with either 17β-estrodiol or estrone increases the activity of Akt and its downstream anabolic signalling proteins, GSK, p70s6k and 4E-BP1 and decreases its catabolic stimulating targets, FOXO, atrogin-1 and MuRF-1. A secondary aim was to determine if this was associated with an increased rate of protein synthesis.

C2C12 myotubes were incubated at 37°C in serum free DMEM without phenol red containing 10 000 units/ml penicillin, 10 000 μg/ml streptomycin, and 250μg/ml amphotericin B for 24h. Myotubes were then stimulated with 17-β estradiol (10nM) for 24h. Phosphorylated and total proteins for Akt, p70S6k, GSK3β, 4E-BP1, FOXO and atrogin-1 were measured using western blotting techniques. Atrogin-1 and MuRF1 mRNA levels were measured using real time-PCR. Protein synthesis rates were measured by incorporation of [3H]-tyrosine into the myotubes during the last hour of treatment.

Compared to control myotubes, treatment with 17β-estradiol increased the ratio of phosphorylated to total protein contents for Akt, GSK-3β and P70s6k by, 1.62, 1.53 and 2.2 fold, respectively (n=6 per group; p < 0.05). There was, however, no difference in the ratios of phosphorylated to total 4E-BP1 or Foxo3a or Atrogin-1 and MuRF1 mRNA. Protein synthesis rates remained unchanged.

This study demonstrates that in C2C12 mouse myotubes, 17β-estradiol treatment increases the phosphorylation of the hypertrophy signalling protein, Akt, and its downstream hypertrophy signalling targets, GSK-3β and P70s6k; no associated changes in protein synthesis were observed. Future studies should investigate the ability of 17β-estradiol to activate these proteins in a model of myotube catabolism and to determine if protein degradation is attenuated.