Unaltered left ventricular mechanics and remodelling after 12 weeks of resistance exercise training – a longitudinal study in men

Previous longitudinal studies suggest that left ventricular (LV) structure is unaltered with resistance exercise training (RT) in young men. However, evidence from aerobic exercise training suggests that early changes in functional LV wall mechanics may occur prior to and independently of changes in LV size, although short-term changes in LV mechanics and structural remodelling in response to RT protocols have not been reported. Therefore, the purpose of this study was to examine the effects of RT on LV mechanics in healthy men performing 2 different time-under-tension protocols. Forty recreationally trained men (age: 23 ± 3 years) were randomized into 12 weeks of whole-body higher-repetition RT (20–25 repetitions/set to failure at ∼30%–50% 1 repetition maximum (1RM); n = 13), lower-repetition RT (8–12 repetitions/set to failure at ∼75%–90% 1RM; n = 13), or an active control period (n = 14). Speckle tracking echocardiography was performed at baseline and following the intervention period. Neither RT program altered standard measures of LV volumes (end-diastolic volume, end-systolic volume, or ejection fraction; P > 0.05) or indices of LV mechanics (total LV twist, untwisting rate, twist-to-shortening ratio, untwisting-to-twist ratio, or longitudinal strain; P > 0.05). This is the first longitudinal study to assess both LV size and mechanics after RT in healthy men, suggesting a maintenance of LV size and twist mechanics despite peripheral muscle adaptations to the training programs. These results provide no evidence for adverse LV structural or functional remodelling in response to RT in young men and support the positive role of RT in the maintenance of optimal cardiovascular function, even with strenuous RT

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells-newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies

The Impact of Step Reduction on Muscle Health in Aging: Protein and Exercise as Countermeasures

Declines in strength and muscle function with age—sarcopenia—contribute to a variety of negative outcomes including an increased risk of: falls, fractures, hospitalization, and reduced mobility in older persons. Population-based estimates of the loss of muscle after age 60 show a loss of ~1% per year while strength loss is more rapid at ~3% per year. These rates are not, however, linear as periodic bouts of reduced physical activity and muscle disuse transiently accelerate loss of muscle and declines in muscle strength and power. Episodic complete muscle disuse can be due to sickness-related bed rest or local muscle disuse as a result of limb immobilization/surgery. Alternatively, relative muscle disuse occurs during inactivity due to illness and the associated convalescence resulting in marked reductions in daily steps, often referred to as step reduction (SR). While it is a “milder” form of disuse, it can have a similar adverse impact on skeletal muscle health. The physiological consequences of even short-term inactivity, modeled by SR, show losses in muscle mass and strength, as well as impaired insulin sensitivity and an increase in systemic inflammation. Though seemingly benign in comparison to bed rest, periodic inactivity likely occurs, we posit, more frequently with advancing age due to illness, declining mental health and declining mobility. Given that recovery from inactivity in older adults is slow or possibly incomplete we hypothesize that accumulated periods of inactivity contribute to sarcopenia. Periodic activity, even in small quantities, and protein supplementation may serve as effective strategies to offset the loss of muscle mass with aging, specifically during periods of inactivity. The aim of this review is to examine the recent literature encompassing SR, as a model of inactivity, and to explore the capacity of nutrition and exercise interventions to mitigate adverse physiological changes as a result of SR

Potato Protein Isolate Stimulates Muscle Protein Synthesis at Rest and with Resistance Exercise in Young Women

Skeletal muscle myofibrillar protein synthesis (MPS) increases in response to protein feeding and to resistance exercise (RE), where each stimuli acts synergistically when combined. The efficacy of plant proteins such as potato protein (PP) isolate to stimulate MPS is unknown. We aimed to determine the effects of PP ingestion on daily MPS with and without RE in healthy women. In a single blind, parallel-group design, 24 young women (21 ± 3 years, n = 12/group) consumed a weight-maintaining baseline diet containing 0.8 g/kg/d of protein before being randomized to consume either 25 g of PP twice daily (1.6 g/kg/d total protein) or a control diet (CON) (0.8 g/kg/d total protein) for 2 wks. Unilateral RE (~30% of maximal strength to failure) was performed thrice weekly with the opposite limb serving as a non-exercised control (Rest). MPS was measured by deuterated water ingestion at baseline, following supplementation (Rest), and following supplementation + RE (Exercise). Ingestion of PP stimulated MPS by 0.14 ± 0.09 %/d at Rest, and by 0.32 ± 0.14 %/d in the Exercise limb. MPS was significantly elevated by 0.20 ± 0.11 %/d in the Exercise limb in CON (p = 0.008). Consuming PP to increase protein intake to levels twice the recommended dietary allowance for protein augmented rates of MPS. Performance of RE stimulated MPS regardless of protein intake. PP is a high-quality, plant-based protein supplement that augments MPS at rest and following RE in healthy young women

Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise

Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 (mTORC1-Raptor positive) regulates skeletal muscle growth, whereas mTORC2 (Rictor positive) regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilised immunohistochemical analysis to study the localisation of mTOR complexes prior to and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in unilateral exercise model. In basal samples, mTOR and the lysosomal marker LAMP2 were highly co-localized and remained so throughout. In the FED and EXFED states, mTOR/LAMP2 complexes were redistributed to the cell periphery (WGA positive staining) (time effect; p=.025), with 39\% (FED) and 26\% (EXFED) increases in mTOR/WGA association observed 1h post-feeding/exercise. mTOR/WGA colocalisation continued to increase in EXFED at 3h (48\% above baseline) whereas colocalisation decreased in FED (21\% above baseline). A significant effect of condition (p=.05) was noted suggesting mTOR/WGA co-localization was greater during EXFED. This pattern was replicated in Raptor/WGA association, where a significant difference between EXFED and FED was noted at 3h post-exercise/feeding (p=.014). Rictor/WGA colocalization remained unaltered throughout the trial. Alterations in mTORC1 cellular location coincided with elevated S6K1 kinase activity, which rose to a greater extent in EXFED compared to FED at 1h post-exercise/feeding (p<.001), and only remained elevated in EXFED at the 3h time point (p=.037). Collectively these data suggest that mTORC1 redistribution within the cell is a fundamental response to resistance exercise and feeding, whereas mTORC2 is predominantly situated at the sarcolemma and does not alter localisation

In-season nutrition strategies and recovery modalities to enhance recovery for basketball players: a narrative review

Basketball players face multiple challenges to in-season recovery. The purpose of this article is to review the literature on recovery modalities and nutritional strategies for basketball players and practical applications that can be incorporated throughout the season at various levels of competition. Sleep, protein, carbohydrate, and fluids should be the foundational components emphasized throughout the season for home and away games to promote recovery. Travel, whether by air or bus, poses nutritional and sleep challenges, therefore teams should be strategic about packing snacks and fluid options while on the road. Practitioners should also plan for meals at hotels and during air travel for their players. Basketball players should aim for a minimum of 8 h of sleep per night and be encouraged to get extra sleep during congested schedules since back-to back games, high workloads, and travel may negatively influence night-time sleep. Regular sleep monitoring, education, and feedback may aid in optimizing sleep in basketball players. In addition, incorporating consistent training times may be beneficial to reduce bed and wake time variability. Hydrotherapy, compression garments, and massage may also provide an effective recovery modality to incorporate post-competition. Future research, however, is warranted to understand the influence these modalities have on enhancing recovery in basketball players. Overall, a strategic well-rounded approach, encompassing both nutrition and recovery modality strategies, should be carefully considered and implemented with teams to support basketball players’ recovery for training and competition throughout the season

An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10–7 for rs4675569, 1.7 × 10–6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P \u3c.05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P \u3c.05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P \u3c.05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology

Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells—newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies

Molecular Transducers of Human Skeletal Muscle Remodeling under Different Loading States

Loading of skeletal muscle changes the tissue phenotype reflecting altered metabolic and functional demands. In humans, heterogeneous adaptation to loading complicates the identification of the underpinning molecular regulators. A within-person differential loading and analysis strategy reduces heterogeneity for changes in muscle mass by ∼40% and uses a genome-wide transcriptome method that models each mRNA from coding exons and 3′ and 5′ untranslated regions (UTRs). Our strategy detects ∼3–4 times more regulated genes than similarly sized studies, including substantial UTR-selective regulation undetected by other methods. We discover a core of 141 genes correlated to muscle growth, which we validate from newly analyzed independent samples (n = 100). Further validating these identified genes via RNAi in primary muscle cells, we demonstrate that members of the core genes were regulators of protein synthesis. Using proteome-constrained networks and pathway analysis reveals notable relationships with the molecular characteristics of human muscle aging and insulin sensitivity, as well as potential drug therapies