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Frontiers in Nutrition 2024It is unclear whether resistance training in combination with different timing of protein intake might have differential effects on muscle hypertrophy, strength, and...
BACKGROUND
It is unclear whether resistance training in combination with different timing of protein intake might have differential effects on muscle hypertrophy, strength, and performance. Therefore, we compared the effects of 8 weeks of resistance training combined with two different high-protein diet strategies (immediately pre-and after, or 3 h pre and after exercise) in resistance-trained males.
METHODS
Forty resistance-trained males (24 ± 4 years) performed 8 weeks of resistance training combined with 2 g kg d protein. Body composition, muscular performance, and biochemical markers were assessed pre and post-intervention.
RESULTS
Nine participants (four from 3 h group and five from the immediate group) withdrew from the study. Therefore, 31 participants completed the study. All measures of skeletal muscle mass, Australian pull-up, and muscle strength, significantly increased post-intervention in both groups ( < 0.05). The biochemical marker urea also significantly increased from pre to post in both groups ( < 0.05). There were no significant between-group differences ( > 0.05).
CONCLUSION
High-protein diet enhances muscular performance and skeletal muscle mass in resistance-trained males, irrespective of intake time. Consequently, the total daily protein intake appears to be the primary factor in facilitating muscle growth induced by exercise.
PubMed: 38846541
DOI: 10.3389/fnut.2024.1397090 -
Sports Medicine - Open Jun 2024Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal...
The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial.
BACKGROUND
Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training.
METHODS
The primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults. In a randomized, controlled, double-blinded trial, 52 untrained, recreationally active participants aged 18-35 y were allocated to either the PEA or PLA groups. Participants consumed either 2 × 175 mg Levagen + PEA or identically matched maltodextrin capsules during an 8-week period of whole-body resistance training. This trial assessed the pre- to post- changes in total and regional lean body mass, muscular strength (1-RM bench, isometric mid-thigh pull), muscular power [countermovement jump (CMJ), bench throw], pain associated with exercise training, sleep, and wellbeing compared with the PEA or PLA condition.
RESULTS
48 Participants were included in the final intention to treat (ITT) analysis and we also conducted per protocol (PP) analysis (n = 42). There were no significant between-group differences for total or regional lean muscle mass post-intervention. There was a significantly higher jump height (CMJ) at week 10 in the PEA group compared to the PLA (Adjusted mean difference [95% CI] p-value; ITT: - 2.94 cm [- 5.15, - 0.74] p = 0.010; PP: - 2.93 cm [- 5.31, - 0.55] p = 0.017). The PLA group had higher 1-RM bench press post-intervention compared with the PEA group (ITT: 2.24 kg [0.12, 4.37] p = 0.039; PP: 2.73 kg [0.40, 5.06] p = 0.023). No significant treatment effects were noted for any of the other outcomes.
CONCLUSION
PEA supplementation, when combined with 8 weeks of strength training, did not impair lean mass gains and it resulted in significantly higher dynamic lower-body power when compared with the PLA condition.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).
PubMed: 38844675
DOI: 10.1186/s40798-024-00732-6 -
Journal of the American Heart... Jun 2024The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal...
BACKGROUND
The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes.
METHODS AND RESULTS
We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity.
CONCLUSIONS
We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.
Topics: Animals; Mineralocorticoid Receptor Antagonists; Renal Insufficiency, Chronic; Naphthyridines; Ventricular Dysfunction, Left; Male; Disease Models, Animal; Fibrosis; Nitric Oxide Synthase Type III; Glomerular Filtration Rate; Ventricular Function, Left; Diastole; Kidney; Phosphorylation; Myocardium; Rats, Sprague-Dawley; Rats; Nephrectomy
PubMed: 38842271
DOI: 10.1161/JAHA.123.032971 -
IScience Jun 2024The routine need for myonuclear turnover in skeletal muscle, together with more sporadic demands for hypertrophy and repair, are performed by resident muscle stem cells...
The routine need for myonuclear turnover in skeletal muscle, together with more sporadic demands for hypertrophy and repair, are performed by resident muscle stem cells called satellite cells. Muscular dystrophies are characterized by muscle wasting, stimulating chronic repair/regeneration by satellite cells. Here, we derived and validated transcriptomic signatures for satellite cells, myoblasts/myocytes, and myonuclei using publicly available murine single cell RNA-Sequencing data. Our signatures distinguished disease from control in transcriptomic data from several muscular dystrophies including facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy, and myotonic dystrophy type I. For FSHD, the expression of our gene signatures correlated with direct counts of satellite cells on muscle sections, as well as with increasing clinical and pathological severity. Thus, our gene signatures enable the investigation of myogenesis in bulk transcriptomic data from muscle biopsies. They also facilitate study of muscle regeneration in transcriptomic data from human muscle across health and disease.
PubMed: 38840844
DOI: 10.1016/j.isci.2024.109947 -
Channels (Austin, Tex.) Dec 2024Alterations in ion channel expression and function known as "electrical remodeling" contribute to the development of hypertrophy and to the emergence of arrhythmias and...
Alterations in ion channel expression and function known as "electrical remodeling" contribute to the development of hypertrophy and to the emergence of arrhythmias and sudden cardiac death. However, comparing current density values - an electrophysiological parameter commonly utilized to assess ion channel function - between normal and hypertrophied cells may be flawed when current amplitude does not scale with cell size. Even more, common routines to study equally sized cells or to discard measurements when large currents do not allow proper voltage-clamp control may introduce a selection bias and thereby confound direct comparison. To test a possible dependence of current density on cell size and shape, we employed whole-cell patch-clamp recording of voltage-gated sodium and calcium currents in Langendorff-isolated ventricular cardiomyocytes and Purkinje myocytes, as well as in cardiomyocytes derived from trans-aortic constriction operated mice. Here, we describe a distinct inverse relationship between voltage-gated sodium and calcium current densities and cell capacitance both in normal and hypertrophied cells. This inverse relationship was well fit by an exponential function and may be due to physiological adaptations that do not scale proportionally with cell size or may be explained by a selection bias. Our study emphasizes the need to consider cell size bias when comparing current densities in cardiomyocytes of different sizes, particularly in hypertrophic cells. Conventional comparisons based solely on mean current density may be inadequate for groups with unequal cell size or non-proportional current amplitude and cell size scaling.
Topics: Myocytes, Cardiac; Animals; Cell Size; Cardiomegaly; Mice; Male; Patch-Clamp Techniques
PubMed: 38836323
DOI: 10.1080/19336950.2024.2361416 -
International Journal of Sports... 2024The rotator cuff (RC) plays a pivotal role in the performance and health of the shoulder and upper extremity. Blood flow restriction training (BFRT) is a modality to...
BACKGROUND
The rotator cuff (RC) plays a pivotal role in the performance and health of the shoulder and upper extremity. Blood flow restriction training (BFRT) is a modality to improve strength and muscle hypertrophy with even low-load training in healthy and injured individuals. There is minimal evidence examining its effect proximal to the occluded area, and particularly on the RC.
HYPOTHESIS & PURPOSE
The purpose of this case series is to explore the effects of low-load BFRT on RC strength, hypertrophy, and tendon thickness in asymptomatic individuals.
STUDY DESIGN
Case series.
METHODS
Fourteen participants with asymptomatic, untrained shoulders were recruited to participate. They performed an eight-week low-load shoulder exercise regimen where BFR was applied to the dominant arm only during exercise. The dependent variables were maximal isometric strength of the shoulder external rotators(ER) and elevators (in the scapular plane in full can position) (FC) measured via handheld dynamometry, cross sectional area (CSA) of the supraspinatus and infraspinatus muscles, and supraspinatus tendon thickness measured via ultrasound imaging (US). Mean changes within and between arms were compared after training using paired t-tests. Cohen's d was used to determine effect sizes.
RESULTS
All participants were able to complete the BFRT regimen without adverse effects. Mean strength and CSA increased for all variables in both arms, however this increase was only significant (p\<0.01) for FC strength bilaterally and CSA for the supraspinatus and infraspinatus on the BFRT side. The effect sizes for increased supraspinatus and infraspinatus CSA on the BFRT side were 0.40 (9.8% increase) and 0.46 (11.7% increase) respectively. There were no significant differences when comparing the mean changes of the BFRT side to the non-BFRT side for strength or muscle CSA. There were no significant changes to supraspinatus tendon thickness.
CONCLUSION
These results suggest variability in response of the RC musculature to low-load BFRT in asymptomatic individuals. The potential for a confounding systemic response in the study design makes determining whether low-load BFRT is more beneficial than low-load non-BFRT difficult. The hypertrophy seen on the BFRT side warrants further study.
LEVEL OF EVIDENCE
4.
PubMed: 38835981
DOI: 10.26603/001c.118143 -
Nature Communications Jun 2024Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In...
Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.
Topics: Animals; Male; Nuclear Receptor Subfamily 4, Group A, Member 1; Energy Metabolism; Mice; Glucagon-Like Peptides; Heart Failure; Mice, Inbred C57BL; Ventricular Remodeling; Lipid Metabolism; Myocytes, Cardiac; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Myocardium; Signal Transduction; Mitochondria; Cardiomegaly
PubMed: 38834564
DOI: 10.1038/s41467-024-48970-2 -
Journal of Animal Science Jan 2024Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the effect of Zn and steroidal implants on performance, trace mineral status, circulating...
Influence of steroidal implants and zinc sulfate supplementation on growth performance, trace mineral status, circulating metabolites, and transcriptional changes in skeletal muscle of feedlot steers.
Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the effect of Zn and steroidal implants on performance, trace mineral status, circulating metabolites, and transcriptional changes occurring in skeletal muscle. Steers (n = 6 per pen) were stratified by body weight (BW) in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (steer as experimental unit; n = 24 per treatment). Dietary treatments (ZINC; eight pens per treatment) included supplemental Zn as ZnSO4 at 1) 0 (analyzed 54 mg Zn/kg DM; Zn0); 2) 30 mg/kg DM (Zn30); 3) 100 mg Zn/kg DM (Zn100). After 60 d of Zn treatment, steers received a steroidal implant treatment (IMP) on day 0: 1) no implant; NO; or 2) high-potency combination implant (TE-200, Elanco, Greenfield, IN; 200 mg TBA, 20 mg E2; TE200). BWs were taken at days -60, 0, and in 28 d increments thereafter. Liver biopsies for TM analysis and blood for TM, serum glucose, insulin, nonesterified fatty acids (NEFA), urea-N, and IGF-1 analysis were collected on days 0, 20, 40, and 84. Glucose, NEFA, and insulin were used to calculate the revised quantitative insulin sensitivity check index (RQUICKI). Linear and quadratic effects of ZINC were evaluated in SAS 9.4. Means for IMP were separated using the LSMEANS statement with the PDIFF option. Day -60 BW was a covariate for performance and carcass data. Growth performance, plasma, liver, and metabolite data were analyzed as repeated measures. TE200 tended to decrease plasma Zn by 8.4% from days 0 to 20 while NO decreased by 3.6% (IMP × day; P = 0.08). A tendency for a ZINC × day effect on G:F was noted (P = 0.06) driven by Zn30 and Zn100 decreasing significantly from period 0-28 to period 28-56 while Zn0 was similar in both periods. An IMP × day effect was noted for RQUICKI where (P = 0.02) TE200 was greater on day 40 compared to NO cattle, but by day 84 RQUICKI was not different between TE200 and NO. On day 20, increasing Zn supplementation linearly increased mRNA abundance (P ≤ 0.09) of protein kinase B (AKT1), mammalian target of rapamycin (mTOR), matrix metalloproteinase 2 (MMP2), and myogenic factor 5 (MYF5). In this study, Zn and implants differentially affected genes related to energy metabolism, satellite cell function, and TM homeostasis on days 20 and 84 postimplant. These results suggest steroidal implants increase demand for Zn immediately following implant administration to support growth and may influence insulin sensitivity in finishing cattle.
Topics: Animals; Cattle; Male; Muscle, Skeletal; Dietary Supplements; Trace Elements; Zinc Sulfate; Drug Implants; Diet; Animal Feed; Trenbolone Acetate
PubMed: 38828800
DOI: 10.1093/jas/skae154 -
Experimental and Therapeutic Medicine Jul 2024Meteorin-β (Metrnβ) is a protein that is secreted by skeletal muscle and adipose tissue, and participates in cardiovascular diseases. However, its role in myocardial...
Meteorin-β (Metrnβ) is a protein that is secreted by skeletal muscle and adipose tissue, and participates in cardiovascular diseases. However, its role in myocardial infarction (MI) has not been fully elucidated to date. The aim of the present study was to investigate the role and underlying mechanism of Metrnβ in MI. In the present study, mice were subjected to left coronary ligation to induce a MI model before being injected with adeno-associated virus 9 (AAV9)-Metrnβ to overexpress Metrnβ. Mice were subjected to echocardiography and pressure-volume measurements 2 weeks after ligation. Cardiac injury was measured from the levels of cardiac troponin T and pro-inflammatory factors, which were detected using ELISA kits. Cardiac remodelling was determined from the cross-sectional areas detected using H&E and wheat germ agglutinin staining as well as from the transcriptional levels of hypertrophic and fibrosis markers detected using reverse transcription-quantitative PCR. Cardiac function was detected using echocardiography and pressure-volume measurements. In addition, H9c2 cardiomyocytes were transfected with Ad-Metrnβ to overexpress Metrnβ, before being exposed to hypoxia to induce ischaemic injury. Apoptosis was determined using TUNEL staining and caspase 3 activity. Cell inflammation was detected using ELISA assays for pro-inflammatory factors. Autophagy was detected using LC3 staining and assessing the protein level of LC3II using western blotting. H9c2 cells were also treated with rapamycin to induce autophagy. It was revealed that Metrnβ expression was reduced in both mouse serum and heart tissue 2 weeks post-MI. Metrnβ overexpression using AAV9-Metrnβ delivery reduced the mortality rate, decreased the infarction size and reduced the extent of myocardial injury 2 weeks post-MI. Furthermore, Metrnβ overexpression inhibited cardiac hypertrophy, fibrosis and inflammation post-MI. In ischaemic H9c2 cells, Metrnβ overexpression using adenovirus also reduced cell injury, cell death and inflammatory response. Metrnβ overexpression suppressed MI-induced autophagy . Following autophagy activation using rapamycin , the protective effects induced by Metrnβ were reversed. Taken together, these results indicated that Metrnβ could protect against cardiac dysfunction post-MI in mice by inhibiting autophagy.
PubMed: 38827476
DOI: 10.3892/etm.2024.12582 -
IScience Jun 2024Hypertension is a major cause of morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM), suggesting a potential role for mechanics in HCM...
Hypertension is a major cause of morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM), suggesting a potential role for mechanics in HCM pathogenesis. Here, we developed an physiological model to investigate how mechanics acts together with HCM-linked myosin binding protein C (MYBPC3) mutations to trigger disease. Micro-heart muscles (μHM) were engineered from induced pluripotent stem cell (iPSC)-derived cardiomyocytes bearing MYBPC3 mutations and challenged to contract against substrates of different elasticity. μHMs that worked against substrates with stiffness at or exceeding the stiffness of healthy adult heart muscle exhibited several hallmarks of HCM, including cellular hypertrophy, impaired contractile energetics, and maladaptive calcium handling. Remarkably, we discovered changes in troponin C and T localization in MYBPC3 μHM that were entirely absent in 2D culture. Pharmacologic studies suggested that excessive Ca intake through membrane-embedded channels underlie the observed electrophysiological abnormalities. These results illustrate the power of physiologically relevant engineered tissue models to study inherited disease with iPSC technology.
PubMed: 38827401
DOI: 10.1016/j.isci.2024.109954