bims-ensmum 2026-11-01 papers

bims-ensmum

Biomed News

on Exercise and nutrition in skeletal muscle metabolism

Issue of 2026–11–01
ten papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht

Corn protein alone, or in blends, stimulates muscle protein synthesis comparable to milk protein, with or without resistance exercise, in older adults.
Non-steady-state modelling reveals reduced skeletal muscle protein synthesis as the primary driver of disuse-atrophy in young, healthy females.
Preserved anabolic skeletal muscle capacity in response to exercise and protein intake after critical illness.
Progesterone does not modulate myofibrillar protein synthesis at rest or following acute resistance exercise in premenopausal females.
Midlife time-restricted feeding preserves skeletal muscle insulin responsiveness and function during aging.
Cold fluid ingestion does not enhance exogenous carbohydrate oxidation during prolonged endurance exercise in the heat.
The Relationship Between Skeletal Muscle Mitochondrial Function and Cardiac Workload During Exercise in Young Healthy Subjects.
Acute Sodium Bicarbonate Supplementation Enhances 10-km Outdoor Track Running Performance in Recreational Female Runners.
Adipocyte lipolysis is a determinant of skeletal muscle size during fasting and feeding.
Longitudinal Analysis of Skeletal Muscle and Cardiometabolic Risk During the Menopause Transition.

J Nutr. 2026 Oct 26. pii: S0022-3166(26)00544-4. [Epub ahead of print] 101895

Corn protein alone, or in blends, stimulates muscle protein synthesis comparable to milk protein, with or without resistance exercise, in older adults.

Changhyun Lim, Matthew J Lees, Tom A H Janssen, James McKendry, Cassady Smith, Matthew Ho, Adam Sutoski, Yulan Wu, Ellika Greaves, Fulvia P da Costa, Meenadshi Varanan, Joy P B Goessens, Joan M Senden, Luc J C van Loon, Stuart M Phillips.

   BACKGROUND: Due to their lower essential amino acid contents, particularly leucine, plant-derived proteins are generally considered to have lower muscle anabolic capacity than animal-based proteins. Corn protein is unique in having a relatively high leucine content; however, its anabolic effects have not been examined in older adults, who exhibit reduced anabolic sensitivity.
OBJECTIVE: We examined the effect of corn protein isolate, a pea and corn protein blend, milk protein isolate, or a non-protein low-energy placebo on muscle protein synthesis (MPS), with or without resistance exercise, in older adults.
METHODS: In a double-blind, placebo-controlled, randomized parallel group trial, 48 healthy older adults (68 ± 5 years; 24 males and 24 females) underwent a primed continuous infusion of L-[ring-13C6] phenylalanine to estimate MPS using the precursor-product approach. Each participant performed unilateral knee extension exercise (3 sets of 10 repetitions at 75% of one-repetition maximum) and consumed 20 g of either corn protein (CORN), a pea and corn protein blend (PEA+CORN), milk protein (MILK), or a non-protein low-energy placebo (PLA). Blood and muscle samples were collected throughout.
RESULTS: The increase in MPS relative to basal values was greater in CORN (216 ± 170%; P < 0.001), PEA+CORN (217 ± 167%; P = 0.001), and MILK (138 ± 78%; P = 0.033) compared with PLA (77 ± 46%), with no differences between groups. Resistance exercise further increased MPS compared with supplementation alone in all groups (all, P < 0.001).
CONCLUSIONS: Ingestion of 20 g corn protein, a pea and corn protein blend, or milk protein increased MPS rates in healthy older adults, and resistance exercise further enhanced the anabolic response. This trial was registered at clinicaltrials.gov as NCT05917223.

Keywords:  Anabolic sensitivity; Plant-sourced protein; Plant-sourced protein blends; Sarcopenia; Stable isotope tracer

DOI:  https://doi.org/10.1016/j.tjnut.2026.101895
J Physiol. 2026 Oct 27.

Non-steady-state modelling reveals reduced skeletal muscle protein synthesis as the primary driver of disuse-atrophy in young, healthy females.

Callum J Pufahl, Jonathan C Mcleod, Emily J Ferguson, Kristine Boileau, Brendan Ross, Thomas R Tripp, Jennifer A Wilkinson, Craig A Simpson, Brendon J Gurd, Chris McGlory.

  Skeletal muscle mass reflects the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). In healthy humans, a decline in MPS is recognized as the primary driver of muscle disuse-atrophy, with limited contribution from increased MPB. However, disuse-induced declines in protein pool size directly influence the calculation of muscle protein turnover. We examined how accounting for changes in protein pool size impacted MPS and MPB rates assessed using deuterium oxide in healthy humans. Fourteen females (21 ± 2 years of age; 24.5 ± 3.0 kg/m2) had one leg subjected to 10 days of unloading, whilst the contralateral leg underwent loading in the form of resistance exercise. Steady-state and non-steady-state modelling approaches were used to calculate MPS and MPB rates. In response to unloading, there was a significant decline in MRI-derived vastus lateralis volume, and thus non-steady-state equations were applied exclusively to this limb. Regardless of whether steady-state or non-steady-state approaches were applied, mixed MPS rates were significantly reduced in response to unloading, whilst mixed MPB rates remained unchanged. Notably, unloading elicited protein fraction-specific responses, whereby myofibrillar MPS rates declined significantly whilst sarcoplasmic MPS rates were unaltered. We also found that in response to loading, mixed, myofibrillar and sarcoplasmic MPS rates remained unchanged compared with basal rates. Our findings show that unilateral unloading in females induces muscle disuse-atrophy driven by reductions in MPS rates, rather than by elevations in MPB rates, a response that was protein fraction specific and preserved irrespective of whether steady-state or non-steady-state equations were used. KEY POINTS: In humans, short-term muscle disuse-atrophy is generally attributed to reduced muscle protein synthesis (MPS) rates, but integrated tracer approaches to measure protein turnover can be influenced by changes in protein pool size. We used deuterated water (2H2O) to measure rates of MPS and muscle protein breakdown (MPB) during 10 days of unilateral unloading in young, healthy females. Steady-state and non-steady-state equations were applied to account for changes in the protein pool size that occur with disuse-atrophy. Unloading reduced muscle size and MPS rates, whereas MPB rates were unchanged. Accounting for the change in the protein pool size using non-steady-state equations did not alter this conclusion. These findings refine our interpretation of the mechanisms driving muscle disuse-atrophy in healthy humans that might differ from more severe clinical or preclinical scenarios of muscle wasting.

Keywords:  exercise; muscle atrophy; skeletal muscle; stable isotope

DOI:  https://doi.org/10.1113/JP292118
Crit Care. 2026 Oct 24. pii: 549. [Epub ahead of print]30(1):

Preserved anabolic skeletal muscle capacity in response to exercise and protein intake after critical illness.

Arabella Fischer-Hammerschmied, Nicolas Tardif, Mirko Mandić, Thomas Gustafsson, William Apro, Johan Helleberg, Mariam Amouzandeh, Jonathan Grip, Dag Seldén, Olav Rooyackers, Martin Sundström Rehal.

   BACKGROUND: Low muscle mass and persistent weakness are common after critical illness, but the mechanisms behind impaired recovery are incompletely understood. The aim of this study was to investigate the skeletal muscle anabolic response to combined resistance exercise and protein intake in intensive care unit (ICU) survivors, compared to matched controls without a history of critical illness. We hypothesised that residual anabolic resistance limits muscle regeneration after ICU stay.
METHODS: Former patients were enrolled within 3 to 6 months of intensive care unit discharge. Muscle biopsies were obtained before and after resistance exercise using a flywheel leg extension ergometer, combined with ingestion of 24 g hydrolysed protein. Muscle protein fractional synthetic rate was determined from the incorporation of [ring-²H₅]phenylalanine into mixed-muscle protein during a primed continuous intravenous infusion. Anabolic and proteolytic pathways were measured using standard assays. Group-by-time differences were analysed using linear mixed models. The primary comparison was the between-group difference in pre-to-post change in muscle protein synthesis.
RESULTS: Twenty ICU survivors (60 ± 12 years, 30% female, BMI 26.9 (IQR 22.9-28.7), SAPS 3 62.3 ± 15.8) and 20 age- and sex-matched controls were included. ICU survivors had significantly lower quadriceps muscle thickness (p = 0.02) and handgrip strength (p = 0.04) than controls. In ICU survivors, muscle protein synthesis from plasma precursor amino acids was higher at baseline than in controls (0.041%/hour vs. 0.030%/hour, p = 0.009), but increased less (Δ 0.031 vs. Δ 0.040%/hour, p = 0.04). Post-intervention muscle protein synthesis was similar between groups (0.071%/hour vs. 0.070%/hour, p = 0.70). At baseline, ICU survivors showed lower activation of the autophagy-lysosomal pathway. In both groups, the intervention increased anabolic signalling, decreased initiation of autophagy and increased parts of the ubiquitin-proteasome pathway.
CONCLUSIONS: In ICU survivors with persistent muscle loss and weakness, the increase in muscle protein synthesis after combined resistance exercise and protein intake was smaller than in controls, in the context of a higher baseline fractional synthetic rate. Post-intervention muscle protein synthesis rates were similar between groups. These findings provide the first mechanistic support for structured exercise-nutrition rehabilitation to promote muscle recovery after critical illness.
TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov (NCT05261984), 2022-02-20.

Keywords:  Anabolism; Critical illness; Muscle protein synthesis; Rehabilitation; Resistance training

DOI:  https://doi.org/10.1186/s13054-026-06418-7
J Physiol. 2026 Oct 23.

Progesterone does not modulate myofibrillar protein synthesis at rest or following acute resistance exercise in premenopausal females.

Alysha C D'Souza, Alison K Shea, Caroline B Dunlop, Matthew J Lees, Hafsa Ali, Dax Houtkamp, Joel L Prowting, James P Newbold, Stuart M Phillips.

  Progesterone has been proposed to modulate skeletal muscle protein turnover, although direct support for this hypothesis is lacking. We examined whether acute elevation of progesterone alters myofibrillar protein synthesis (MyoPS) at rest and following resistance exercise (RE) in naturally menstruating females. Twenty premenopausal females (21 ± 3 years of age) were randomised in a double-blind, placebo-controlled trial to receive oral micronized progesterone (400 mg) or matching placebo at -34 and -10 h before a stable isotope infusion on days 1-5 of their menstrual cycle. One leg performed RE while the contralateral leg remained rested, followed by ingestion of 30 g whey protein. MyoPS was quantified using the l-[ring-1 3C6]-phenylalanine precursor-product method across fasted-rested, fed-rested and fed-exercised conditions. Progesterone elevated serum concentrations well above the luteal-phase range (185 ± 105 vs. 1.0 ± 0.2 ng mL-1). Despite this, we detected no difference in MyoPS groups in any conditions, including the exercise-induced increment (treatment × leg interaction, P = 0.945). Both protein feeding (P = 0.00459) and RE (P < 0.001) independently stimulated MyoPS above resting fasted levels. Progesterone was associated with modestly lower total amino acid concentrations, but not essential amino acid or leucine specifically; postprandial kinetics did not differ between groups. Acute elevation of circulating progesterone above the luteal-phase range does not detectably modify the skeletal muscle anabolic response to RE or protein feeding in premenopausal females. These findings challenge the characterisation of progesterone as catabolic (or anabolic) to skeletal muscle and indicate that menstrual cycle phase-based training recommendations predicated on a progesterone-driven effect warrant critical re-evaluation. KEY POINTS: Progesterone has been proposed to exert catabolic effects on skeletal muscle, yet direct evidence in premenopausal adult females is absent. We examined whether pharmacological elevation of progesterone augments myofibrillar protein synthesis (MyoPS) at rest and following resistance exercise. Oral micronized progesterone administered at 34 and 10 h before testing successfully elevated serum progesterone to well above the luteal-phase range (185 ± 105 vs. 1.0 ± 0.2 ng mL-1) during the early follicular phase. Despite this, MyoPS did not differ between progesterone and placebo in fasted-rested, fed-rested or fed-exercised conditions. Resistance exercise robustly elevated MyoPS above the fed-rested conditions, confirming model sensitivity. Neither postprandial amino acid availability nor individual progesterone exposure was associated with MyoPS. These findings challenge the characterisation of progesterone as pro-catabolic/anti-anabolic to skeletal muscle and indicate that menstrual cycle phase-based training and nutrition recommendations predicated on progesterone-driven effects on skeletal muscle are not supported by direct mechanistic evidence.

Keywords:  female; menstrual cycle; progesterone; protein synthesis; resistance exercise; skeletal muscle

DOI:  https://doi.org/10.1113/JP292285
Am J Physiol Cell Physiol. 2026 Nov 01. 331(5): C1506-C1520

Midlife time-restricted feeding preserves skeletal muscle insulin responsiveness and function during aging.

Raz Ben-David, Nikita Sarvin, Eli Carmeli, Nitsan Dahan, Tomer Shlomi, Shenhav Shemer.

  Primary sarcopenia, the progressive loss of skeletal muscle mass and function during aging, is partly driven by anabolic resistance, a reduced ability of aged muscle to activate protein synthesis in response to nutrients and hormones. We compared 12-wk time-restricted feeding (TRF) and alternate-day fasting (ADF) interventions initiated at 3, 12, 15, or 18 mo of age in male C57BL/6J mice (analyzed at 6, 15, 18, or 21 mo, respectively). The effects of intermittent fasting on skeletal muscle were strongly age-dependent. Midlife (15 mo of age) TRF preserved lean mass, improved glucose tolerance, and increased insulin-stimulated glucose uptake in isolated muscle, whereas ADF induced broader metabolic remodeling but was associated with lean-tissue loss when initiated later in life. Muscle aging was accompanied by reduced membrane abundance of insulin receptor-plakoglobin-dystrophin glycoprotein complex (DGC) signaling assembly. However, midlife TRF was associated with greater abundance of these protein modules and enhanced postprandial AKT signaling. These findings identify midlife as a responsive window for nutritional timing interventions and link improved muscle insulin responsiveness and maintenance with diet-associated differences in sarcolemmal protein abundance and organization, although targeted perturbation studies are required to establish causality.NEW & NOTEWORTHY Midlife time-restricted feeding preserved lean mass, muscle performance, glucose tolerance, and insulin-stimulated glucose uptake in male mice. These physiological benefits were accompanied by greater membrane abundance of selected components of the insulin receptor-plakoglobin-DGC signaling assembly and enhanced postprandial AKT signaling. The data reveal an age-sensitive response to nutritional timing but do not establish a causal connection between preservation of this assembly and the physiological improvements.

Keywords:  anabolic resistance; dystrophin glycoprotein complex; insulin signaling; sarcopenia; time-restricted feeding

DOI:  https://doi.org/10.1152/ajpcell.00315.2026
J Appl Physiol (1985). 2026 Nov 01. 141(5): 1301-1311

Cold fluid ingestion does not enhance exogenous carbohydrate oxidation during prolonged endurance exercise in the heat.

Loïs Mougin, Ben Will, Coen C W G Bongers, Lewis J James, Stephen A Mears.

  This study investigated the effects of ingesting cold versus warm carbohydrate beverages on exogenous carbohydrate oxidation and time-trial performance during prolonged cycling in the heat. Eleven trained, non heat-acclimated cyclists [21 ± 3 yr; 69.3 ± 8.3 kg; peak oxygen uptake ([Formula: see text]): 64.7 ± 5.0 mL/kg/min] completed two trials comprising 100 min of submaximal cycling at 50% Wpeak followed by a time trial in a hot environment (36.2 ± 0.3°C; 55 ± 3% relative humidity). Participants ingested a 15% dextrose solution enriched with [U-13C] glucose (60 g/h; bolus every 20 min) provided either cold (COLD; 4.0 ± 1.6°C) or at room temperature (WARM; 35.8 ± 0.5°C). Heart rate and rectal temperature were lower in COLD than in WARM during the 100-min exercise (P ≤ 0.006), whereas skin temperature did not differ between conditions. Average (40-100 min) exogenous carbohydrate oxidation (COLD: 0.50 ± 0.10 vs. WARM: 0.51 ± 0.10 g/min; P = 0.80), peak exogenous carbohydrate oxidation, total carbohydrate and fat oxidation, and blood glucose, lactate, and insulin concentrations did not differ between trials (all P ≥ 0.34). Sweat losses and body mass changes were unaffected by condition (P ≥ 0.40). Time-trial performance was not different between COLD and WARM (P = 0.38). Despite attenuating cardiovascular and thermal strain, ingesting a cold carbohydrate beverage during exercise in the heat did not enhance exogenous carbohydrate oxidation, substrate utilization, or performance compared with a warm beverage.NEW & NOTEWORTHY This study showed that, despite reducing cardiovascular and thermal strain, ingesting a cold (4°C) versus warm (36°C) carbohydrate beverage did not enhance exogenous carbohydrate oxidation, substrate utilization, or time-trial performance during prolonged cycling in the heat. These findings suggest that beverage temperature is not a relevant factor for optimizing carbohydrate availability during exercise under heat stress, and that athletes can select beverage temperature based on palatability and preference rather than for metabolic benefit.

Keywords:  cooling; stable isotope; substrate metabolism; thermal strain; thermoregulation

DOI:  https://doi.org/10.1152/japplphysiol.00617.2026
Eur J Sport Sci. 2026 Nov;pii: e70267. [Epub ahead of print]26(11):

The Relationship Between Skeletal Muscle Mitochondrial Function and Cardiac Workload During Exercise in Young Healthy Subjects.

Tommi Jeskanen, Venla P Ylinen, Rasmus I P Valtonen, Ville Stenbäck, Kari A Mäkelä, Risto Kerkelä, Juhani M Junttila, Noora Pöllänen, Riikka Kivelä, Kalle Kolari, Eija Pirinen, Karl-Heinz Herzig, Mikko P Tulppo.

  Exaggerated cardiac workload responses to incremental exercise are associated with the development of hypertension and future cardiovascular events. We hypothesized that skeletal muscle mitochondrial function is associated with cardiac workload, quantified as Rate Pressure Product (RPP), during exercise. Healthy adults (n = 18; 9 females; age 25 ± 4 years) performed a maximal exercise test on a cycle ergometer. The test began at 0 W and followed an incremental protocol starting at 40 W, with load increases every 2 minutes until exhaustion. Breath-by-breath gas exchange was measured to determine peak oxygen uptake and the respiratory compensatory point (RCP). Heart rate (HR) and systolic blood pressure (BP) were recorded at each load to calculate RPP. The cardiac workload response to exercise was defined as the change in RPP from 0 W to the intensity corresponding to RCP (ΔRPP). Muscle biopsies from the vastus lateralis were collected on separate days to assess mitochondrial respiration. ΔRPP from 0 W to RCP intensity was 18181 ± 2147 mmHg·bpm and Complex I mediated respiration was 31.9 ± 13.7 pmol·mg-1 s-1. ΔRPP was correlated only with Complex I (r = -0.69, p = 0.002) and sex (r = 0.50, p = 0.035). In a forward stepwise linear regression analysis with ΔRPP as the dependent variable and baseline RPP, sex, and complex I mediated respiration as predictors, complex I mediated respiration was the only variable significantly associated with ΔRPP (adjusted R2 = 0.44; unstandardized β = -107; 95% CI:-167 to -47; p = 0.002). The cardiac workload response to exercise is strongly associated with skeletal muscle mitochondrial function in young normotensive individuals.

Keywords:  blood pressure; cardiac workload; exercise; mitochondrial function; mitochondrial respiration

DOI:  https://doi.org/10.1002/ejsc.70267
Int J Sport Nutr Exerc Metab. 2026 Oct 23. 1-11

Acute Sodium Bicarbonate Supplementation Enhances 10-km Outdoor Track Running Performance in Recreational Female Runners.

Selin Aktitiz, Yasemin Güzel, Muhammed Mustafa Atakan, Süleyman Bulut, Yiğitcan Karanfil, Andrew M Jones, Hüseyin Hüsrev Turnagöl.

  This study investigated the effects of acute sodium bicarbonate (SB) supplementation co-ingested with a carbohydrate-rich meal on 10-km running performance and gastrointestinal symptoms in recreational female runners under field-based conditions. Twenty-one healthy women (33.6 ± 4.6 years; body mass index 20.8 ± 1.3 kg/m; maximal oxygen uptake 48.6 ± 2.0 ml·kg-1·min-1) completed two 10-km outdoor track running time trials (TTs) in a randomized, double-blind, crossover design. Participants ingested either SB (0.3 g/kg body mass [BM]) or placebo (PLA; 0.03 g/kg BM table salt), together with a standardized carbohydrate-rich meal (1.5 g/kg BM), 90 min before exercise during the same phase of the menstrual cycle. Blood pH, bicarbonate [HCO3-], and [lactate] were measured before, and 1, 3, 5, and 7 min after the TTs; performance time was recorded. Gastrointestinal symptoms were recorded at 30, 60, and 90 min after SB and PLA ingestions. Blood pH (7.47 ± 0.03 vs. 7.42 ± 0.04, p < .001) and [HCO3-] (27.7 ± 1.4 vs. 22.2 ± 1.5 mmol/L, p < .001) were higher at rest and remained elevated postexercise following SB compared with PLA (p < .05 for all time points). TT completion time improved after SB compared with PLA (3,046.1 ± 208.7 s vs. 3,078.4 ± 206.8 s; p = .011). No significant differences in gastrointestinal symptoms scores were observed between conditions (p > .05 for all). In conclusion, acute co-ingestion of 0.3 g/kg of SB with a carbohydrate-rich meal is a practical and well-tolerated strategy to achieve higher resting blood [HCO3-] and pH as well as to improve 10-km TT running performance in recreational female runners.

Keywords:  acid–base balance; aerobic capacity; buffering capacity; ergogenic aids; gastrointestinal symptoms

DOI:  https://doi.org/10.1123/ijsnem.2026-0041
Am J Physiol Endocrinol Metab. 2026 Nov 01. 331(5): E562-E571

Adipocyte lipolysis is a determinant of skeletal muscle size during fasting and feeding.

Daniel M Marko, Rhea V Vemula, Meghan O Conn, Nazli Robin, Angela M Schmidt, Irena A Rebalka, Jonathan D Schertzer.

  Intermittent fasting (IF) can lower fat mass, but also muscle mass. The mechanisms governing tissue partitioning during fasting remain unclear. During fasting, adipose-derived fatty acids from lipolysis and lipolysis-fueled hepatic ketogenesis maintain blood glucose and systemic energy homeostasis. We hypothesized that impaired lipolysis during fasting would shift substrate provision from adipose to muscle, increasing muscle catabolism during IF. We tested male adipocyte-specific adipose triglyceride lipase knockout (aKO) and littermate floxed-control mice during ad libitum feeding on a 10-wk 5:2 IF protocol consisting of two nonconsecutive 24-h fasts and 5 ad libitum feeding days per week. After 10 wk of IF, aKO mice had lower blood lipids and ketones and lost more lean mass and less fat mass than floxed-control mice when mice were fed a standard control diet and also retained more inguinal white adipose tissue and had lower hindlimb muscle mass when IF was compared with ad libitum feeding. In addition, aKO mice had larger adipocytes, smaller muscle fibers, and increased expression of the atrogene, Atrogin1. We then provided exogenous lipids by feeding an obesogenic high-fat diet (HFD). HFD-fed aKO mice had higher whole body fat oxidation and lower blood lipids and ketones than floxed-controls. Obese HFD-fed aKO mice still had smaller skeletal muscle myofibers and increased muscle atrogene expression despite smaller adipocytes during ad libitum feeding or IF. Therefore, adipocyte ATGL-mediated lipolysis is a determinant of skeletal muscle size, and lower lipolysis influences the balance of fat vs. muscle loss during fasting.NEW & NOTEWORTHY This study demonstrates that adipocyte ATGL is a critical regulator of adipose-muscle metabolic crosstalk. Limiting adipocyte lipolysis through adipose ATGL deletion reduced blood lipid and ketone fuel availability, thereby increasing adipose retention, decreasing skeletal muscle mass and fiber size, and increasing muscle atrogene expression, particularly during intermittent fasting. These findings support a model in which impaired adipocyte lipid mobilization shifts whole body energy demands away from adipose and toward skeletal muscle, promoting muscle catabolism during fasting.

Keywords:  ATGL; intermittent fasting; lipolysis; obesity

DOI:  https://doi.org/10.1152/ajpendo.00262.2026
Am J Physiol Endocrinol Metab. 2026 Oct 23.

Longitudinal Analysis of Skeletal Muscle and Cardiometabolic Risk During the Menopause Transition.

Hannah E Cabre, Kaja Falkenhain, Steve R Smith, Catherine M Champagne, Fanchao Yi, Jennifer C Lovejoy, Leanne M Redman.

  We assessed longitudinal changes in body composition and cardiometabolic risk in those with normal-weight and overweight/obese women across the menopausal transition. We examined a 10-year longitudinal analysis of 81 healthy women in the prospective Healthy Transitions cohort. Body composition measures were obtained via dual-energy X-ray absorptiometry. Skeletal muscle was estimated using a validated prediction model: 1.12 × appendicular lean mass- 0.63. Serum sex steroid hormones and cardiometabolic factors were quantified in fasting blood. Participants were stratified by BMI into normal weight (n=41) and overweight/obesity (n=40) groups. Changes within and between BMI groups across the menopause transition were assessed with linear mixed models. At menopause onset, compared to those with normal weight, participants with overweight/obesity had lower sex hormone-binding globulin (-30.9±10.3 nmol/L; p=0.01), greater percent body fat (13.1±1.3%; p<0.001), greater skeletal muscle mass (2.5±0.6 kg; p<0.001), and worse cardiometabolic risk factors (p<0.001). In the 5 years before menopause, participants with overweight/obesity gained skeletal muscle (+1.2 kg) and fat mass (+3.5 kg), while participants with normal weight increased percent body fat (+1.5%) only. At menopause onset, women with overweight/obesity exhibit distinct alterations in body composition, hormonal profiles, and cardiometabolic risk that exist in the years preceding menopause, highlighting the importance of early, targeted interventions to mitigate adverse health trajectories during the menopause transition.

Keywords:  Estrogen; Healthy Transitions; fat-free mass; normal weight; obesity

DOI:  https://doi.org/10.1152/ajpendo.00173.2026