bims-ensmum Biomed News
on Exercise and nutrition in skeletal muscle metabolism
Issue of 2026–11–08
seven papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht
  1. An integrative multi-omic analysis of skeletal muscle in response to disuse and recovery resistance training in resistance trained and untrained young adults.
  2. Leg glucose uptake and substrate utilisation during time trial exercise: Effects of acute hypobaric hypoxia and biological sex.
  3. Effect of a training camp in the heat on nutritional intake of well-trained endurance athletes.
  4. GLP-1 and GIP receptor agonism does not directly drive skeletal muscle atrophy or impair myogenesis in primary human myotubes.
  5. Proteomic Interrogation of the Acute Response to Muscle Damage in Untrained Middle Aged and Older Females.
  6. Dietary threonine requirement of healthy older adults >60y stratified by age and sex in a repeated measures design1.
  7. Differentiated obesity treatment: Pharmacological CRF2 agonism drives fat loss, skeletal muscle hypertrophy and improved glucose metabolism in preclinical obesity.
  1. Skelet Muscle. 2026 Aug 05. pii: 40. [Epub ahead of print]16(1):
    An integrative multi-omic analysis of skeletal muscle in response to disuse and recovery resistance training in resistance trained and untrained young adults.
    J Max Michel, Joshua S Godwin, Zachary A Graham, Jacob A Siedlik, Melissa D Boersma, Martino V Franchi, Harsimran S Baweja, C Brooks Mobley, Andreas N Kavazis, David C Hughes, Marcas M Bamman, Michael D Roberts, Christopher G Vann.
      We previously reported that resistance trained (T) and untrained (UT) individuals exhibit similar targeted molecular responses in skeletal muscle following two weeks of leg immobilization and eight weeks of subsequent recovery resistance training (RT). The present analysis examined the skeletal muscle transcriptome, microRNA (miR)-ome, and proteome responses in a subset of these participants (N = 8 T and N = 8 UT). Vastus lateralis biopsies were obtained at baseline (PRE), after the 2-wk immobilization protocol (DIS), and after 8-wk of recovery RT (REC-RT). Tissue RNA and protein were subjected to RNA- and miR-sequencing and proteomics, respectively. Analyses included: (i) group and time differential expression (DE) and pathway enrichment for each independent -ome; (ii) multi-omics integration to reveal modules across the -omes; and (iii) leave one out cross-validated linear regression modeling (LOOCV) to reveal key features predictive of atrophy and hypertrophy. Most differentially expressed (DE) RNAs or differentially abundant (DA) proteins were time-driven rather than training status-driven. In all participants, the transcriptome was most responsive to disuse (PRE-to-DIS: 2047 DE mRNAs; 3 DE miRs; 10 DA proteins) while the transcriptome and proteome were both responsive to recovery RT (DIS-to-REC-RT: 446 DE mRNAs; 0 DE miR; 415 DA proteins). Pathways analyses revealed proteostasis and DNA repair with disuse atrophy, whereas striated muscle contraction, transcriptional regulation, and rRNA expression were enriched with recovery RT. Integrative analyses identified SLIT-ROBO signaling as a potentially novel axis in disuse atrophy, driven predominantly by transcriptomic changes, whereas enrichment of striated muscle contraction pathways in recovery RT was supported by coordinated mRNA and protein regulation. Via LOOCV, the 10 top predictors of disuse atrophy were RNAs (8 protein coding) primarily related to mitochondrial function and protein trafficking, while 9 of the top 10 predictors of recovery RT hypertrophy were RNAs (8 protein coding) related to membrane dynamics, ECM/cytoskeletal organization, and translation initiation. This integrative multi-omic approach reiterates that disuse atrophy and recovery RT-induced hypertrophy elicit similar molecular responses in T and UT individuals, highlighting distinct molecular signatures governing skeletal muscle atrophy and recovery hypertrophy independent of training status.
    Keywords:  Atrophy; Disuse; Hypertrophy; Integrative networks; Proteomics; RNA-seq; miRNA
    DOI:  https://doi.org/10.1186/s13395-026-00440-7
  2. J Physiol. 2026 Nov 05.
    Leg glucose uptake and substrate utilisation during time trial exercise: Effects of acute hypobaric hypoxia and biological sex.
    Anders Aagaard Hansen, Marcos Martin-Rincon, Bjarne Rud, Jacob Marcus Egebjerg, Daniel Wüstner, Niels Ørtenblad, Robert Boushel, Hans-Christer Holmberg, Jose A L Calbet, Jostein Hallén, Joachim Nielsen, Øyvind Skattebo.
      Hypoxia reduces exercise performance, yet it remains unclear how biological sex and altitude influence substrate utilisation during prolonged maximal exercise. Twenty-two trained cyclists and triathletes (10 females) completed 30 min time trials (TTs) at low altitude (normoxia; ∼400 m) and moderate altitude (hypoxia; ∼2800 m in a hypobaric chamber) in counterbalanced order. Whole-body metabolism was estimated from indirect calorimetry, whereas leg glucose uptake and substrate utilisation were derived from arterial and femoral venous blood samples and leg blood flow (thermodilution). Muscle biopsies were obtained from vastus lateralis to measure glycogen utilisation. Across altitudes, females displayed a higher fractional utilisation of V̇O2max during the TTs. TT performance was decreased in hypoxia, and the proportional decrease was smaller in females (-14%) than in males (-18%). Whole-body substrate utilisation was similar between sexes in normoxia. However, males showed a large decrease in carbohydrate oxidation in hypoxia, whereas females displayed only a modest decrease. Males and females had similar leg metabolic responses to hypoxia: estimated glycogen oxidation decreased, with no change in absolute fat or blood glucose oxidation. However, across altitudes, females showed greater carbohydrate contributions, originating primarily from blood glucose rather than muscle glycogen. Estimates of fat contribution were uncertain but suggested a lower contribution in females than in males. In conclusion, females exercised at a higher relative intensity and derived relatively more energy from blood glucose. Males and females had similar leg metabolic responses to hypoxia, with the lower power output and metabolic rate in hypoxic TTs primarily regulated by reduced estimated glycogen oxidation. KEY POINTS: Substrate utilisation during exercise is affected by altitude, sex, training status, food intake and relative intensity. Whether sex- and altitude-related differences in substrate utilisation persist during an ecologically valid maximal time trial in the fed state in trained males and females is unknown. Acute hypobaric hypoxia (∼2800 m) decreased 30 min time trial performance compared to normoxia (∼400 m) in both sexes, with a larger decrement in males. Females completed the time trials at a higher relative intensity than males in normoxia and hypoxia. Hypoxia reduced total metabolic rate primarily by decreasing estimated muscle glycogen oxidation, with no change in fat or blood glucose oxidation. The resulting changes in substrate partitioning were similar between sexes. Across altitudes, females derived relatively more energy from blood glucose despite similar muscle glycogen utilisation between sexes, whereas uncertain estimates suggested a lower contribution of fat in females than in males.
    Keywords:  altitude; carbohydrate metabolism; cycling; endurance performance; fat oxidation; glucose uptake; hypoxia; metabolism; muscle glycogen; sex differences; substrate utilisation; thermodilution; time trial
    DOI:  https://doi.org/10.1113/JP291982
  3. J Sports Sci. 2026 Nov 02. 1-12
    Effect of a training camp in the heat on nutritional intake of well-trained endurance athletes.
    Eve Tiollier, Marina Fabre, Julien Louis, Yann Le Meur, Cyril Schmit, Paul Robach, Laurie-Anne Marquet, Christophe Hausswirth.
      We investigated the effect of a training camp in the heat on energy and macronutrient intake and hunger. Twenty-two athletes completed two training periods (8 days each) of similar load. One group (HEAT, n = 14) trained successively in a temperate environment (10 ± 3°C, RH: 58 ± 11 %) and then in a hot environment (30 ± 5°C, RH: 74 ± 15%), while the other group (CON, n = 8) trained in the same temperate environment. Daily energy intake (EI), carbohydrate (CHO) and protein (PRO) intake were higher (p < 0.001) in HEAT (+23.9 ± 20.3%, +36.1 ± 24.3%, +27.5 ± 21.2%, respectively) during the heat camp compared with the temperate condition. More specifically, EI, CHO and PRO intake were greater at breakfast in HEAT (+90.1 ± 65.5%, +107.2 ± 74.3%, +69.8 ± 54.1 %, respectively). PRO intake also increased at dinner (p < 0.001) in HEAT. Mean EI and macronutrient intake during the training sessions were significantly increased (p < 0.01) in HEAT. Hunger was greater before breakfast in HEAT (p < 0.01) during the heat camp. In CON, none of the measures differed between the two training periods. These results suggest that athletes spontaneously increase their energy intake when training in the heat, with breakfast serving as the primary meal for this nutritional adjustment.
    Keywords:  Tropical climate; appetite; carbohydrate; dietary intake; energy
    DOI:  https://doi.org/10.1080/02640414.2026.2754629
  4. Geroscience. 2026 Nov 04.
    GLP-1 and GIP receptor agonism does not directly drive skeletal muscle atrophy or impair myogenesis in primary human myotubes.
    Caitlin Ditchfield, Michael Macleod, Joshua M J Price, Edward T Davis, Simon W Jones.
      GLP-1 and GIP/GLP-1 receptor agonists produce substantial weight loss in clinical trials but significant loss of lean body mass is reported. Whether this reflects a direct pharmacological effect on skeletal muscle or an indirect consequence of caloric restriction and reduced mechanical loading is unknown. Primary myoblasts were isolated from skeletal muscle of older adults with obesity undergoing orthopaedic surgery. GIPR and GLP-1R expression was characterised by RT-qPCR and flow cytometry. Differentiated myotubes were treated with semaglutide or GIP peptide and assessed for atrophy-related gene expression (qPCR), secretome perturbation (Olink Reveal), mitochondrial and glycolytic bioenergetics (Seahorse XF Real-Time ATP Rate Assay, glucose uptake, lactate secretion) and myotube morphology and myogenesis (immunofluorescence). GIPR mRNA was consistently detected across all donors; GLP-1R mRNA was undetectable by PCR, though LUXendin645 flow cytometry in a subset of three donors identified low-level surface GLP-1R protein in 51-66% of myoblasts. Neither semaglutide nor GIP altered atrophy-related gene expression or the secretome, with no proteins reaching significance. Semaglutide reduced glycolytic and total ATP production rates, accompanied by reduced lactate secretion, suggesting modest suppression of glycolytic flux; mitochondrial parameters were unaffected. Neither treatment impaired myotube thickness or differentiation; GIP increased myotube thickness after 8 days. Direct GLP-1 and GIP receptor activation did not produce major atrophic, inflammatory, morphological, myogenic, or mitochondrial effects on primary human skeletal muscle myotubes. These findings are consistent with an indirect mechanism underlying the lean mass loss observed with incretin-based therapies, a question of particular relevance as these agents are increasingly used in older adults at risk of sarcopenia.
    Keywords:  GIP receptor; GLP-1 receptor; Incretins; Muscle atrophy; Sarcopenia; Semaglutide
    DOI:  https://doi.org/10.1007/s11357-026-02625-w
  5. J Appl Physiol (1985). 2026 Nov 02.
    Proteomic Interrogation of the Acute Response to Muscle Damage in Untrained Middle Aged and Older Females.
    J Max Michel, Sophia C Bamman, Franccesco P Boeno, S Craig Tuggle, Kana Meece, Amritpal Kaur, Jacob A Siedlik, Zachary A Graham, Marcas M Bamman.
      Blunted regenerative responses to muscle damage with aging are linked to inflammatory signaling and satellite cell dynamics; however, most evidence is derived from males and is limited to targeted assays of bulk muscle tissue and/or circulating biomarkers. Here, we focused on middle-aged and older females and leveraged multi-compartment proteomics to identify responses to modest muscle damage across myofibrillar (MYOF), sarcoplasmic (SARCO), and serum compartments. Sixteen females (mean age = 61±8 years) had vastus lateralis biopsies and serum collected before (PRE) and 24 h after (POST) a resistance loading protocol that induced modest muscle damage (72.9% increase in serum creatine kinase activity). SARCO and MYOF fractions were separated using differential centrifugation, and proteomics was performed on three compartments using a nanoparticle capture approach followed by mass spectrometry, yielding 9,059 proteins in SARCO, 4,334 in MYOF, and 3,964 in serum. The protocol produced 90 differentially abundant (DA) proteins in SARCO (61 up, 29 down), 39 in MYOF (27 up, 12 down), and 124 in serum (34 up (9 muscle-specific), 90 down). DA proteins minimally overlapped across compartments. Enrichment analyses pointed primarily to translation-related processes in MYOF and contractile processes in serum. Pathway Level Information ExtractoR performed on all DA proteins identified multi-compartment biocircuits linked to membrane trafficking, vesicle mediated transport, neutrophil degranulation, and viral infection. Viral infection-related proteins correlated with body weight and body fat, while vesicle mediated transport-related proteins correlated with serum creatine kinase activity. This analysis reveals novel biocircuitry of modest muscle damage in middle-aged and older females.
    Keywords:  Proteomics; biocircuits; females; muscle damage
    DOI:  https://doi.org/10.1152/japplphysiol.90213.2026
  6. Am J Clin Nutr. 2026 Oct 31. pii: S0002-9165(26)00428-4. [Epub ahead of print] 101619
    Dietary threonine requirement of healthy older adults >60y stratified by age and sex in a repeated measures design1.
    Alyssa Paoletti, Wala Naeem, Paul B Pencharz, Christopher Tomlinson, Mahroukh Rafii, Dehan Kong, Bingqing Li, Rajavel Elango, Glenda Courtney-Martin.
       BACKGROUND: Current dietary guidelines for most of the world recommend increased plant protein consumption to improve health and support environmental sustainability. Threonine is an indispensable AA required for protein and mucin synthesis which is present in low concentrations in plant proteins. Threonine requirement is needed to guide dietary planning and assessment of protein adequacy particularly in those consuming predominantly plant-based protein diets. However, no data exist on dietary threonine requirement in older adults.
    OBJECTIVES: 1) Determine the threonine requirement in older adults using the indicator amino acid oxidation (IAAO) method in a repeated measures design. 2) compare the derived estimates based on age: 60-69y and 70-79y and sex.
    METHODS: The threonine requirement was determined using the IAAO method with L-[1-13C] phenylalanine as the indicator. Twenty-two older adults >60 y (n = 10 males and n = 12 females) were randomly assigned to receive up to 7 threonine intakes (5 to 35 mg/kg/d). The mean threonine requirement was determined from oxidation of L-[1-13C] phenylalanine (F13CO2) using a two-phase linear mixed effect model. The 95% CI was calculated using parametric bootstrap. The overlap of the 95% CI between the 2 age groups were used to compare the requirement estimates. The null hypothesis was accepted if the interval contained zero.
    RESULTS: There was no effect of sex on the threonine requirement. However, the threonine requirement for adults 60-69y and 70-79y were 11 mg/kg/d (R2m = 0.10, R2c = 0.81; 7.70, 14.30 mg/kg/d) and 17.9 mg/kg/d (R2m = 0.44, R2c = 0.64; 13.23, 22.57 mg/kg/d) respectively with those 70-79y having a higher requirement than those 60-69y ( -1.18, -12.62).
    CONCLUSIONS: The result of the current study demonstrates that AA needs among older adults change within decades of age. This should be integrated into future AA recommendations for accurate planning and assessment of protein nutrition in the elderly. The trial was registered at Clinical Trials Registry: # NCT02008955, https://clinicaltrials.gov/study/NCT06225648.
    Keywords:  Amino acid requirement; Elderly; Indicator amino acid oxidation; Stable isotopes; Threonine
    DOI:  https://doi.org/10.1016/j.ajcnut.2026.101619
  7. Mol Metab. 2026 Oct 31. pii: S2212-8778(26)00152-3. [Epub ahead of print] 102468
    Differentiated obesity treatment: Pharmacological CRF2 agonism drives fat loss, skeletal muscle hypertrophy and improved glucose metabolism in preclinical obesity.
    Kristoffer Niss, Sofia Lundh, Rucha Patel, Johannes Josef Fels, Albrecht Gruhler, Suzi Høgh Madsen, Fabrice Chimienti, Sarah Bau, Dennis Åsberg, Lennart Lykke, Nick Cox, Birgitte S Wulff, Nikolaj Kulahin Roed, Chien Li, Berit Ø Christoffersen.
       OBJECTIVE: Loss of lean mass during weight reduction may compromise metabolic health and physical function. Urocortin 2 (UCN2) activates corticotropin-releasing factor receptor 2 (CRF2) and has been linked to beneficial effects on skeletal muscle and glucose metabolism. We evaluated an acylated UCN2 analogue (acyUCN2), alone or combined with an acylated GLP-1 analogue (acyGLP-1), in preclinical obesity models.
    METHODS: Diet-induced obese (DIO) Sprague Dawley rats and DIO Göttingen Minipigs were treated with vehicle or acyUCN2 (rats, pigs) or acyGLP-1 or combination therapy (rats only). Food intake, body weight (BW), body composition, glucose tolerance and energy expenditure (rats only) were assessed. Histology and RNA-sequencing were used to characterize muscle remodelling and transcriptional responses.
    RESULTS: In rats, acyUCN2 reduced food intake and fat mass, increased lean mass and muscle weight, and improved glucose tolerance despite limited effects on BW. Energy expenditure was not affected. Histology demonstrated hypertrophy across fibre types and a shift from type 2A to type 2X/B fibres. Transcriptomic analyses supported muscle growth and fibre type switch, relative reduced vasculature, regulation of neuromuscular junction-associated genes, and overlap to human acute exercise-response signatures. In obese minipigs, acyUCN2 increased lean mass and improved insulin sensitivity, with modest effects on BW and fat mass, alongside regulation of genes linked to muscle biology and metabolism.
    CONCLUSIONS: Pharmacological CRF2 agonism promotes favourable body composition, muscle hypertrophy, and improved glucose metabolism despite limited weight loss, supporting clinical development of UCN2 analogues as a differentiated obesity treatment, particularly in combination with appetite-regulating therapies and in settings where preservation of functional muscle mass is critical.
    Keywords:  CRF2 agonism; Glucose metabolism; Muscle hypertrophy; Neuromuscular junction; Obesity; Skeletal muscle fibre remodelling; Transcriptomics; Urocortin 2
    DOI:  https://doi.org/10.1016/j.molmet.2026.102468
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