bims-ensmum 2026-09-20 papers

bims-ensmum

Biomed News

on Exercise and nutrition in skeletal muscle metabolism

Issue of 2026–09–20
six papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht

Piperine disrupts the OFF state of the resting thick filament of rat skeletal muscle, enhancing dynamic contractility in a fibre-type-dependent manner.
Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.
Resistance Exercise Training Selectively Modulates Tumor Suppressor and Muscle-Regulatory MicroRNAs in Breast Cancer Survivors and Healthy Postmenopausal Women: An Exploratory Study.
UCI Sports Nutrition Project: Position Statement on Nutrition for Cycling.
Citius, Maius, Melius: Mitochondria and Endurance Performance.
Effects of Clenbuterol on Body Composition and Strength Following Resistance Training, Detraining, and Retraining in Healthy Adults: A Randomized Controlled Trial.

J Physiol. 2026 Sep;604(18): 7739-7771

Piperine disrupts the OFF state of the resting thick filament of rat skeletal muscle, enhancing dynamic contractility in a fibre-type-dependent manner.

Daniel Z Kruse, Jon Herskind, Michel N Kuehn, Annika J Klotz, Anthony L Hessel, Kristian Overgaard.

  The myosin-containing thick filament has been shown to alter its resting structure in response to multiple diseases and therapeutics. Changes in thick filament resting structure are caused by myosin heads transitioning between ordered and disordered OFF conformational states. Functionally, this modulation of thick filament structure is a key regulatory step in muscle contraction and a promising therapeutic target. The availability of disordered myosin heads governs dynamic contractility, which is critical to physical function and well-being. At present, there is a lack of compounds favouring this disordered state in resting skeletal muscle. Piperine is a molecule known to bind to myosin and increase submaximal isometric contractility in fast and slow skeletal muscle. However, the effects on dynamic contractility and the underlying mechanism responsible for the observed effects in skeletal muscles remain unclear. Here, we used fibre small-angle X-ray diffraction and intact-muscle ex vivo contractility experiments to determine the effects of piperine on resting myosin structure and dynamic contractility in fast and slow rat muscles. X-ray diffraction data suggest that piperine promotes a priming of myosin in resting skeletal muscle from an ordered OFF state to a disordered OFF state, increasing the availability of myosin heads for force generation. Functionally, piperine substantially enhanced submaximal dynamic contractility in both muscle types, while only leading to improvements in slow muscle during maximal electrical stimulation. These findings establish piperine as a tool for priming the thick filament in skeletal muscle, highlighting muscle-type-specific effects of thick-filament modulation on the recruitment of the contractile reserve capacity. KEY POINTS: Piperine is a compound known to bind to skeletal muscle myosin and enhance isometric contractility in fast and slow muscles, but its effect on dynamic muscle function and the underlying molecular mechanism remain unknown. We show that piperine disrupts the ordered OFF state of the myosin-containing thick filament in resting fast and slow skeletal muscle, which likely explains the effect of piperine on contractile function. Piperine substantially increases contractile power of both fast and slow skeletal muscles at low-frequency stimulation; however, it only enhances power in slow skeletal muscle at high-frequency stimulation. Our data reveal potentiation of dynamic contractility with fibre-type-dependent magnitudes in response to piperine-induced priming of the resting thick filament, which is a phenomenon requiring further investigation. Dynamic contractility drives locomotion in vivo; therefore, thick-filament priming may ultimately be exploited in the treatment of diseases characterised by skeletal muscle weakness.

Keywords:  contractile power; force–velocity curve; skeletal muscle phenotype; skeletal‐muscle myosin; small‐angle X‐ray diffraction; thick‐filament activation

DOI:  https://doi.org/10.1113/JP290962
J Int Soc Sports Nutr. 2026 Dec 30. 23(1): 2720742

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.

Reza Bagheri, Hamid Ghobadi, Maryam Mansordehghan, Donny M Camera, Mehdi Kargarfard.

   BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2 × 3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO₂max.
METHODS: In this randomized 2 × 3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g·kg-1·d-1. Baseline-adjusted ANCOVA tested training × protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants.
RESULTS: For SMM, no training-condition × protein-target interaction (p = 0.856), marginal protein-target effect (p = 0.726), or marginal training-condition effect (p = 0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p < 0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p < 0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO₂max (adjusted difference, 4.53 mL·kg-1·min-1; 95% CI, 3.80 to 5.25; p < 0.001). No detectable marginal protein-target effects or training-condition × protein-target interactions were observed for the key secondary outcomes.
CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

Keywords:  Exercise training; body composition; muscular adaptations; nutrition

DOI:  https://doi.org/10.1080/15502783.2026.2720742
Int J Mol Sci. 2026 Sep 04. pii: 7900. [Epub ahead of print]27(17):

Resistance Exercise Training Selectively Modulates Tumor Suppressor and Muscle-Regulatory MicroRNAs in Breast Cancer Survivors and Healthy Postmenopausal Women: An Exploratory Study.

Macarena Artigas-Arias, Josefa Bonicioli, Nolberto Huard, Luis A Salazar, Jorge Sapunar, Luis Peñailillo, Denisse Valladares-Ide, Rui Curi, Gabriel Nasri Marzuca-Nassr.

  Progressive resistance exercise training (RET) enhances skeletal muscle mass in healthy postmenopausal women (HEAs) and breast cancer survivors (BCSs) undergoing endocrine therapy. MicroRNAs (miRNAs) are recognized as key epigenetic regulators of exercise-induced adaptations, functioning as tumor suppressors, oncomiRs, and modulators of skeletal muscle homeostasis. Nevertheless, the impact of RET on circulating miRNA profiles in this population remains largely unexplored. This study aimed to explore the effects of a 12-week progressive RET program on plasma miRNAs associated with tumor biology and skeletal muscle regulation in HEAs and BCSs. Five HEAs and five BCSs undergoing endocrine therapy completed a 12-week supervised progressive RET program (3 sessions/week, 60-80% 1RM). Plasma samples were collected before and after intervention, and candidate miRNA expression was quantified by qRT-PCR, normalized to hsa-miR-16-5p, and analyzed using the 2-ΔΔCt method. At baseline, no significant differences were observed between HEA and BCS in tumor suppressor miRNAs (miR-let-7f-5p, miR-125a-5p, miR-342-3p), oncomiRs (miR-21-5p, miR-155-5p, miR-221-3p), or skeletal muscle-related miRNAs (miR-206-3p, miR-486-5p) (p > 0.05). The only exception was miR-375-3p, which showed increased expression in HEA vs BCS (p = 0.037). After 12 weeks of RET, The BCS group showed increases in miR-125a-5p (p = 0.050) and miR-342-3p (p = 0.048) with significant group × time interactions that remained significant after Benjamini-Hochberg False Discovery Rate (BH-FDR) correction (FDR-adjusted p = 0.042 for both). Both groups displayed a nominal increase in miR-375-3p (p = 0.042), which did not remain significant after FDR correction. No significant changes were detected for miR-let-7f-5p or the analyzed oncomiRs in either group. Both miR-206-3p and miR-486-5p exhibited upward trends in the BCS group (p > 0.05). In this exploratory study, 12-week RET program was associated with selective changes in plasma miRNA expression in the HEA and BCS groups, suggesting that this training regimen may act as an epigenetic modulator of circulating miRNAs involved in tumor suppression and skeletal muscle homeostasis.

Keywords:  breast cancer; hormone therapy; microRNAs; strength training

DOI:  https://doi.org/10.3390/ijms27177900
Int J Sport Nutr Exerc Metab. 2026 Sep 15. 1-27

UCI Sports Nutrition Project: Position Statement on Nutrition for Cycling.

Louise M Burke, Eimear Dolan, Javier T Gonzalez, Iñigo Mujika, Asker E Jeukendrup, Martijn Redegeld, Gabriel Martins, Pedro L Valenzuela, Peter Leo, Manuel Mateo-March, Gabriele Gallo, Stephen Seiler, James P Morton, Mark Hearris, Marc J Fell, Daniel J Owens, Shona Halson, Jorn Trommelen, Jamie Stanley, Eric Haakonssen, Jill J Leckey, Kellie Hogan, Kerry O'Bryan, Tanja Oosthuyse, José J Muros, Mikel Zabala, Luuk Hillkens, Jan-Willem van Dijk, Jose L Areta, Megan A Kuikman, Alexandra M Coates, David M Bailey, James Moran, Patrick B Wilson, David B Pyne, Adrian Rotunno, Brendan Egan, Juan Del Coso, Wim Derave, Bryan Saunders, Simon Helleputte, Teun van Erp, Daniel Green, Tim Podlogar, Stephen S Cheung, Lars Nybo, Olivier Girard, Trent Stellingwerff, Dana M Lis, Nicki Strobel, Xavier Bigard, Jamie Whitfield.

  Nutrition is a key determinant of cycling performance, underpinning the ability to optimize on-bike performance, support training adaptation and recovery, and maintain rider health and well-being. While these goals are shared across disciplines, the diverse physiological demands and logistical constraints of different cycling disciplines present distinct nutritional challenges. In recognition of both the importance of nutrition and the diverse individual and discipline-specific demands of cycling, the Union Cycliste Internationale Sports Nutrition Project was established and led by a steering committee that synthesized the expertise of 54 researchers to identify key nutritional requirements for elite cycling and develop recommendations that account for both individual and discipline-specific needs. These insights were published within a series of 14 topic-specific reviews. In this position statement, we present the principal take-home messages from the overall project, organized into 10 overarching themes spanning performance preparation, in-competition fueling, recovery and adaptation, energy availability, physique management, protecting against illness and injury, technological support, the use of supplements and sports foods, and age- and sex-specific considerations. Cycling-specific considerations are used to develop targeted nutritional recommendations within each of these themes, and high-priority future research directions are identified.

Keywords:  endurance athletes; energy availability; ergogenic aids; macronutrients; performance

DOI:  https://doi.org/10.1123/ijsnem.2026-0135
Sports Med. 2026 Sep 12.

Citius, Maius, Melius: Mitochondria and Endurance Performance.

Javier Botella, David J Bishop, Cesare Granata.

Endurance performance relies on a range of physiological adaptations classified as central or peripheral depending on whether the remodeling occurs in the cardiovascular system or in the skeletal muscle, respectively. One of the goals of these adaptations is to enhance oxygen transport and its utilization by mitochondria to sustain ATP resynthesis. While a link between skeletal muscle mitochondrial characteristics and endurance performance may seem obvious, there is no consensus on whether mitochondrial characteristics are key determinants of endurance performance. In this narrative review, we examine cross-sectional, correlational, and intervention studies conducted in humans that support or challenge the role of mitochondria in endurance performance. Cross-section studies suggest that individuals with superior endurance performance exhibit greater mitochondrial content and respiratory function than those with lower fitness levels. Correlation studies have shown positive associations between multiple mitochondrial characteristics and markers of endurance performance. However, a lack of correlation between training-induced changes in mitochondrial characteristics and endurance performance has also been reported. Intervention studies indicate that changes in mitochondrial characteristics following training, phlebotomy, or detraining are often associated with changes in markers of endurance performance. Conversely, increasing oxygen delivery to the working muscle (i.e., via increasing oxygen concentration) has been shown to improve performance markers, suggesting these improvements are not limited by mitochondrial characteristics. In conclusion, while substantial evidence associates mitochondrial characteristics with endurance performance, this relationship is not universal; central factors display an equally strong influence independently of mitochondrial characteristics. We propose that enhanced mitochondrial characteristics represent an important and often necessary, but not sufficient, adaptation that is required to support endurance performance.

DOI: https://doi.org/10.1007/s40279-026-02530-4
Sports Med. 2026 Sep 12.

Effects of Clenbuterol on Body Composition and Strength Following Resistance Training, Detraining, and Retraining in Healthy Adults: A Randomized Controlled Trial.

Lukas Moesgaard, Sebastian Skov Uhrenholt, Søren Jessen, Rasmus Blak Hasgaard, Vibeke Backer, Yvette Dehnes, Jens Bangsbo, Morten Hostrup.

BACKGROUND: Clenbuterol, a potent β2-adrenoceptor agonist, is commonly used off-label in conjunction with resistance training to increase muscle mass and decrease fat mass. However, the long-term effects on body composition and strength with use and following discontinuation of use remain unexplored.
OBJECTIVE: The aim of the study was to investigate the effects of clenbuterol on body composition and strength during a resistance training intervention, as well as the long-term effects of prior use of clenbuterol during detraining and subsequent retraining in healthy young men and women.
METHODS: This randomized, double-blinded, placebo-controlled trial was conducted at the University of Copenhagen, Denmark, between March 2023 and March 2025. Thirty-two healthy men (26 ± 3 years; mean ± SD; n = 16) and women (25 ± 5 years; n = 16) completed 8 weeks of resistance training with daily ingestion of clenbuterol (80 μg) (n = 16) or placebo (n = 16). This was followed by 16 weeks of detraining and another 8 weeks of resistance training. Before the intervention and after each training and detraining period, body composition was assessed by dual-energy X-ray absorptiometry (DXA) and strength was assessed by leg press and bench press 1-repetition maximum (1RM).
RESULTS: Clenbuterol increased gains in lean mass (+ 1.7 kg, p < 0.001) and 1RM bench press (+ 6 kg, p < 0.001) and leg press (+ 16 kg, p = 0.001) during 8 weeks of resistance training compared with placebo, with a more pronounced effect in males than females (lean mass: p = 0.003; 1RM bench press: p < 0.001), whereas the decrease in fat mass did not differ between clenbuterol and placebo (p = 0.614). Following cessation of clenbuterol, detraining decreased lean mass (p < 0.001), 1RM bench press (p < 0.001), and 1RM leg press (p = 0.026) to a greater extent in the clenbuterol group, such that initial changes in lean mass (p = 0.363) and 1RM bench press (p = 0.834) no longer differed from placebo, whereas 1RM leg press remained elevated in the clenbuterol group (p = 0.041). Retraining increased lean mass and 1RM leg press with no differences between the clenbuterol and placebo group (lean mass: p = 0.393; 1RM leg press: p = 0.662), whereas the increase in 1RM bench press was greater in the clenbuterol group (+ 3 kg, p = 0.047).
CONCLUSION: Clenbuterol markedly augments training-induced gains in lean mass and strength. After discontinuation, prior clenbuterol exposure does not enhance retraining-induced lean mass gains, but some strength-related advantages persist.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05692856.

DOI: https://doi.org/10.1007/s40279-026-02522-4