bims-mimead 2025-08-24 papers

bims-mimead

Biomed News

on Adipose tissue and metabolic disease

Issue of 2025–08–24
nine papers selected by
Rachel M. Handy, University of Guelph

Global proteomics reveals distinct muscle adaptations to menstrual cycle phase-based sprint interval training in endurance-trained females.
Effects of a combined energy restriction and vigorous-intensity exercise intervention on the human gut microbiome: A randomised controlled trial.
The effect of rotenone contamination on high-resolution mitochondrial respiration experiments.
Effects of caloric restriction and exercise-induced weight loss on physiological dysregulation in postmenopausal women: The mediating role of fat mass and adipose tissue distribution.
Effects of resistance-based training and polyphenol supplementation on physical function, metabolism, and inflammation in aging individuals.
AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria.
Cardiac CapZ Regulation During Acute Exercise in Female Mice.
Time-restricted feeding combined with exercise improves hepatic and glycaemic metabolism in obese mice: A sex-dependent study.
Activation of mitophagy and proteasomal degradation confers resistance to developmental defects in postnatal skeletal muscle.

Mol Cell Proteomics. 2025 Aug 14. pii: S1535-9476(25)00152-5. [Epub ahead of print] 101053

Global proteomics reveals distinct muscle adaptations to menstrual cycle phase-based sprint interval training in endurance-trained females.

Julie Kissow, Kamine Julie Jacobsen, Søren Jessen, Laura Bachmann Thomsen, Júlia Prats Quesada, Jens Bangsbo, Atul Shahaji Deshmukh, Morten Hostrup.

  Advances in mass-spectrometry (MS)-based technologies have leveraged our understanding of protein-wide adaptations in human skeletal muscle in response to exercise. However, there is a lack of such data in females, particularly pertaining to already trained females and menstrual cycle phase-based sprint interval training (SIT) despite its efficacy and popularity. Here, we present a comprehensive global proteome analysis of skeletal muscle adaptations to high-frequency SIT during different menstrual cycle phases in endurance-trained females. We randomized 49 eumenorrheic females to either high-frequency SIT in the follicular (FB) or luteal phase (LB) over one menstrual cycle comprising eight sessions of 6×30-s all-out efforts. MS-proteomics, covering 4155 proteins after filtering, revealed notable differences in muscle adaptations to phase-based SIT. LB suppressed mitochondrial pathways of the tricarboxylic acid cycle and electron transport chain while enriching ribosomal complexes. Conversely, FB enriched filament organization and skeletal system development. Mitochondrial repression during LB was linked to reduced V˙O2max, whereas exercise capacity improved in FB only. Our findings show that menstrual cycle phase-based high-frequency SIT induces distinct protein-wide muscle adaptations and affects phenotype in endurance-trained eumenorrheic females. CLINICAL TRIAL REGISTRATION NUMBER: NCT04136457.

Keywords:  Athletes; Estrogen; Exercise; Female; Performance; Sex hormones

DOI:  https://doi.org/10.1016/j.mcpro.2025.101053
J Physiol. 2025 Aug 19.

Effects of a combined energy restriction and vigorous-intensity exercise intervention on the human gut microbiome: A randomised controlled trial.

Russell G Davies, Laura A Wood, Aaron Hengist, Ciara O'Donovan, Wiley Barton, Fiona Crispie, Jean-Philippe Walhin, Maria A Valdivia-Garcia, Isabel Garcia-Perez, Gary Frost, Orla O'Sullivan, Paul D Cotter, Javier T Gonzalez, James A Betts, Françoise Koumanov, Dylan Thompson.

  Metabolic health improvements in response to exercise and energy restriction may be mediated by the gut microbiome, yet causal evidence in humans remains limited. We used a 3-week exercise and energy restriction intervention to examine changes to the gut microbiome in otherwise healthy sedentary men and postmenopausal women with overweight/obesity. Intervention participants (n = 18) reduced habitual energy intake by 5000 kcal/week and expended 2000 kcal/week in addition to habitual physical activity through treadmill walking at 70% V̇O2Peak. Control participants (n = 12) maintained their usual lifestyle. Participants underwent dual-energy X-ray absorptiometry (DEXA), and samples of faeces, fasted venous blood, subcutaneous adipose tissue and skeletal muscle were collected. Faecal DNA was sequenced and profiled using shotgun metagenomics, Kraken2/Bracken and Human Microbiome Project Unified Metabolic Analysis Network 2 (HUMAnN2). The intervention significantly reduced body mass (mean Δ ± SD: -2.6 ± 1.5 kg), fat mass (-1.5 ± 1.3 kg), fasted insulin (-23.5 ± 38.1 pmol/l), leptin (-10.6 ± 7.3 ng/ml) and total cholesterol (-0.70 ± 0.42 mmol/l) concentrations, and also improved insulin sensitivity (HOMA2%S (homeostatic model of assessment)). Despite these significant metabolic changes the gut microbiome was unchanged in terms of α and β diversity and relative abundance. Thus, despite clinically meaningful improvements in body composition and metabolic health, we found no evidence for changes to the gut microbiome. In conclusion early metabolic changes with weight loss in humans are unlikely to be mediated by changes to the gut microbiome. KEY POINTS: Changes to the gut microbiome could contribute to metabolic improvements associated with weight loss in humans, but there have been limited attempts to address this question using robust randomised controlled trials (RCTs). We used a parallel-group RCT to examine whether a 3-week combined energy intake restriction and vigorous-intensity exercise intervention in people with overweight and obesity was temporally associated with changes to gut microbiome taxonomic composition and functional potential, short-chain fatty acid concentrations and expression of genes related to host-microbiome interactions in skeletal muscle and subcutaneous adipose tissue. We found that the human gut microbiome remains unchanged in the face of an intensive energy intake restriction and vigorous exercise intervention that significantly improved body composition and metabolic health in people with overweight/obesity. These findings indicate that early metabolic changes with weight loss in humans are unlikely to be mediated by changes to the gut microbiome.

Keywords:  metabolism; microbiome; weight loss

DOI:  https://doi.org/10.1113/JP287424
PeerJ. 2025 ;13 e19879

The effect of rotenone contamination on high-resolution mitochondrial respiration experiments.

Dale F Taylor, Jia Li, Nicholas J Saner, Jia Wei, Xu Yan, Elizabeth G Reisman, Hanzhe Li, Matthew J-C Lee, Navabeh Zare, Andrew Garnham, Jujiao Kuang, David J Bishop.

   Background: High-resolution respirometry is commonly used in skeletal muscle research and exercise science to measure mitochondrial respiratory function in both permeabilized muscle fibers and isolated mitochondria. Due to the low throughput and high cost of the most used respirometer, the Oroboros 2k (O2k), multiple experiments are often conducted within the same chamber in short succession. Despite this, no methodological consideration has been given for the potential contamination of inhibitors, used to investigate the contribution of specific complexes within the electron transport chain, between experiments.
Methods: We first assessed the potential effect of inhibitor contamination on mitochondrial respiration experiments by evaluating the ability of the currently recommended wash protocol to remove rotenone and compared its efficacy against a simplified wash protocol of sequential rinses. Secondly, we assessed the potential effect of inhibitor contamination on mitochondrial respiration measured before and after a single session of high-intensity interval exercise, with and without the use of rotenone between experiments.
Results: The currently recommended protocol for washing chambers was insufficient for removing rotenone. Following exercise, a decrease in mitochondrial respiration was observed exclusively in chambers exposed to rotenone between experiments.
Discussion: Our findings highlight an important methodological consideration regarding the measurement of mitochondrial respiratory function using high-resolution respirometry, with inhibitor contamination potentially affecting the conclusions derived from experiments conducted in close succession. Future studies investigating mitochondrial respiratory function should assess the necessity of using inhibitors such as rotenone, ensure thorough wash procedures between experiments, and explicitly report the washing protocols used.

Keywords:  Bioenergetics; Exercise; Exercise-induced adaptation; Mitochondria; Oroboros O2k; Permeabilized fibers; Protocol development; Respiration; Rotenone

DOI:  https://doi.org/10.7717/peerj.19879
J Nutr Health Aging. 2025 Aug 18. pii: S1279-7707(25)00176-9. [Epub ahead of print]29(9): 100651

Effects of caloric restriction and exercise-induced weight loss on physiological dysregulation in postmenopausal women: The mediating role of fat mass and adipose tissue distribution.

Éloïse Routhier, Martin Brochu, Alan A Cohen, Denis Prudhomme, Ahmed Ghachem.

   BACKGROUND: Physiological dysregulation (PD), quantified through the validated statistical method known as Mahalanobis distance (DM), reflects the progressive breakdown of homeostatic control across multiple, interdependent biological systems. Increasingly recognized as a fundamental hallmark of aging, PD is strongly associated with elevated risks of morbidity and mortality. Despite current knowledge on DM, it remains uncertain whether this metric is sensitive to lifestyle interventions. This gap limits the potential of DM as a responsive marker for monitoring changes in health status over time.
OBJECTIVES: 1) To evaluate the impact of a 6-month caloric restriction (CR) program, either alone or in combination with structured exercise (CR + Ex), on PD. 2) To investigate whether changes in adipose tissue quantity and distribution mediate the effects of these interventions on PD.
METHODS: Data from a total of 102 inactive overweight or obese postmenopausal women (CR: n = 68 vs CR + Ex: n = 34) were studied. Total adipose tissue and its distribution were measured using dual-energy X-ray absorptiometry and computed tomography scan. DM was calculated using 7 blood biomarkers: total cholesterol, HDL-C, LDL-C, triglycerides, C-reactive protein, albumin, and ferritin.
RESULTS: After the interventions, there was a significant decrease in fat mass measurements and plasma level of ferritin (from 38.61 ± 4.60 to 36.35 ± 2.89 ng/mL), albumin (from 63.26 ± 51.08 to 56.43 ± 37.38 g/dL), and triglycerides (from 1.70 ± 0.77 to 1.48 ± 0.76 mmol/L) across the whole sample. However, PD increased for both group after the 6-month period.
CONCLUSION: Despite improvements in specific biomarkers and reductions in fat mass, overall PD increased following the interventions. A non-significant trend toward attenuated dysregulation was observed in the combined CR and exercise group, but changes in adiposity did not significantly mediate this effect, suggesting that other biological mechanisms may underlie the systemic response.

Keywords:  Biological age; Inactive postmenopausal women with obesity; Lifestyle; Mahalanobis distance; Physiological dysregulation

DOI:  https://doi.org/10.1016/j.jnha.2025.100651
Geroscience. 2025 Aug 19.

Effects of resistance-based training and polyphenol supplementation on physical function, metabolism, and inflammation in aging individuals.

Mathias Flensted-Jensen, Cecilie Moe Weinreich, Ann-Sofie Kleis-Olsen, Filip Hansen, Nadia Stenner Skyggelund, Jeppe Rahbek Pii, Ryan Whitlock, Marie-Louise Brødsgaard Abrahamsen, Thomas Isbrandt Petersen, Anders Karlsen, Dace Reihmane, Flemming Dela.

  Aging is associated with declines in muscle mass, strength, aerobic capacity, and metabolic health, accompanied by increased low-grade inflammation. The purpose of this study was to assess the effects of 12 weeks of resistance training (RT) combined with minimal high-intensity interval training (HIIT), with or without polyphenol supplementation, on muscular, cardiovascular, metabolic, and inflammatory adaptations in healthy older adults. Forty-one men and women aged 55-70 years ingested either polyphenol supplementation or placebo for 30 days, then underwent 12 weeks of supervised RT combined with once-weekly HIIT, continuing polyphenol supplementation or placebo throughout. The training intervention increased whole-body and thigh lean mass, vastus lateralis cross-sectional area, type II fiber size, and muscle and functional strength (all p < 0.001). Maximal oxygen uptake significantly increased (p = 0.0001), accompanied by reductions in heart rate and plasma lactate during submaximal exercise, as well as increases in total blood volume and hemoglobin mass (p < 0.05). Training led to reductions in respiratory exchange ratio and plasma cortisol during exercise, which, together with decreased cholesterol levels and trends toward increased peak fat oxidation, may suggest enhanced substrate utilization. Polyphenols alone lowered cholesterol levels but had no other effects. Although no changes were observed in basal systemic or muscle inflammation, the exercise intervention attenuated the acute exercise-induced inflammatory responses of IL-10, IFN-γ, and TNF-α (p < 0.05). These results indicate that a combined RT and minimal HIIT program improves muscular, aerobic, and metabolic health, and may improve inflammatory regulation in aging adults.

Keywords:  Aging; Exercise; Inflammation; Polyphenols; Resistance training

DOI:  https://doi.org/10.1007/s11357-025-01839-8
Cell Death Dis. 2025 Aug 18. 16(1): 623

AMPK regulates ARF1 localization to membrane contact sites to facilitate fatty acid transfer between lipid droplets and mitochondria.

Lupeng Chen, Yue Liu, Junzhi Zhang, Tongxing Song, Jian Wu, Zhuqing Ren.

Lipid droplet (LD) -mitochondrion contacts play a crucial role in regulating energy metabolism and fatty acid oxidation in skeletal muscle cells. However, the proteins that regulate these interactions remain poorly understood. Here, we demonstrate that the binding between ADP-ribosylation factor 1(ARF1) and perilipin2 (Plin2) regulates LD-mitochondrion contacts under starvation conditions, facilitating the transfer of fatty acids from LDs to mitochondria. In C2C12 cells, starvation increased ARF1's GTP-binding activity and its localization to mitochondria, enhancing ARF1's binding to Plin2 and facilitating fatty acid flow from LDs to mitochondria. In contrast, knockdown of ARF1 reduced LD-mitochondrion interactions and blocked fatty acids transfer. Additionally, ARF1-mediated interactions were regulated by AMPK; inhibiting AMPK activity reduced ARF1 localization to LDs and mitochondria, and blocked LD-mitochondrion interactions. In mice, starvation increased ARF1 expression in muscle tissue and LD-mitochondrion contacts. Conversely, inhibiting ARF1 led to lipid accumulation in muscle tissue. In conclusion, our work suggests that ARF1 is a critical regulator of LD-mitochondrion interactions and plays a significant role in energy metabolism regulation in skeletal muscle.

DOI: https://doi.org/10.1038/s41419-025-07957-7
FASEB J. 2025 Aug 31. 39(16): e70950

Cardiac CapZ Regulation During Acute Exercise in Female Mice.

Logan K Townsend, David Wright, W Glen Pyle.

  Exercise requires a rapid cardiac response to maintain cardiovascular function. CapZ is a critical stress-response protein in cardiac myocytes. While its role in the pathological stress response has been explored, its part in the physiological response to exercise is unknown. This study examined CapZ regulation during exercise to determine its importance in the cardiac response. Female wildtype or cardiac CapZ-deficient transgenic mice ("CapZ mice") were subjected to exhaustive swimming or running protocols and submaximal running. Time to exhaustion was a measurement of exercise capacity. Following submaximal exercise, cardiac myofilaments were isolated and probed for CapZ, its regulatory proteins, and myofilament proteins. Myofilament function was assessed using an actomyosin MgATPase assay, and protein phosphorylation was quantified with ProQ Diamond staining. Total myofilament CapZ was unaffected by exercise, but increased CapZIP and decreased phosphorylated CapZIP indicated weakened CapZ-actin interaction. Myofilaments from CapZ mice lacked changes in CapZIP. Time to exhaustion was lower in CapZ mice in both swimming and running protocols. Actomyosin MgATPase activity was maintained in wildtype mice and impaired with CapZ deficiency. Exercise increased myofilament protein phosphorylation in wildtype mice but not in transgenic animals. Exercise-dependent increases in myofilament PKC-α and -ε were mitigated in CapZ mice. Telethonin/Tcap levels decreased significantly in CapZ-deficient myofilaments with exercise, and leiomodin 2 increased in wildtype myofilaments. These data show Cardiac CapZ is a critical player in the physiological response to exercise and that CapZ-actin binding is rapidly altered with exercise. Decreased cardiac CapZ limits exercise capacity, impairs myofilament regulation, and leads to a less stable contractile apparatus.

Keywords:  Z‐discs; actin capping protein; acute exercise; heart; myofibrils

DOI:  https://doi.org/10.1096/fj.202502431R
J Physiol. 2025 Aug 19.

Time-restricted feeding combined with exercise improves hepatic and glycaemic metabolism in obese mice: A sex-dependent study.

Gabriel Calheiros Antunes, Camila Venturini Ayres Cunha, Leandro Kansuke Oharomari, Renan Fudoli Lins Vieira, Maura Fanti, Thaiane da Silva Rios, Luciana Renata Conceição de Mattis, Ana Paula Azevêdo Macêdo, Adelino Sanchez Ramos da Silva, Eduardo Rochete Ropelle, Dennys Esper Cintra, José Rodrigo Pauli.

  Erratic feeding patterns, such as those experienced by shift workers, can exacerbate obesity and metabolic-associated fatty liver disease (MAFLD). Both nutritional factors and sexual dimorphism influence the progression of MAFLD. Time-restricted feeding (TRF) has emerged as a promising strategy to mitigate the effects of obesity, supported by evidence of its benefits for metabolic disorders like MAFLD. Regular physical exercise is also recommended as a non-pharmacological approach to combat obesity and its related conditions. Both TRF and exercise independently show promise in improving metabolic health, weight management and glycaemic control. Thus, combining these approaches may offer a more effective strategy against obesity and MAFLD. In this study, male and female C57BL/6J mice were subjected to an 8-week obesity induction protocol, followed by TRF (16/8) or TRF combined with aerobic exercise. The results showed that TRF, even during the inactive phase of the mice, had positive effects on weight loss, adiposity, glycaemic homeostasis, insulin sensitivity, liver lipid composition, hepatic fat accumulation and the reduction of lipogenic and inflammatory genes in the liver. The combination of TRF with aerobic exercise provided additional benefits, including improved regulation of hepatic triglycerides and respiratory exchange ratio (RER) in males, enhanced fasting glucose levels in females and reduced Fatp4 gene expression in both sexes. Aerobic exercise performance also improved in both sexes, with males achieving superior results. Notably, the combination of TRF with aerobic exercise provided greater metabolic benefits, with sex-specific differences observed in metabolic responses. KEY POINTS: Eight weeks of western diet induced obesity, an impaired glucose homeostasis and increased hepatic fat accumulation in male and female C57BL/6J mice. Time-restricted feeding (TRF) 16/8 in the active phase and TRF combined with aerobic exercise reduced weight gain and metabolic disorders in C57BL/6J male and female mice fed a western diet. TRF when combined with aerobic exercise displayed more pronounced improvements in the hepatic metabolism. TRF when combined with aerobic exercise improved liver triglycerides and respiratory exchange ratio in males, fasting glucose in females and decreased lipogenic gene Fatp4 expression in both males and females.

Keywords:  aerobic exercise; metabolic‐associated fatty liver disease (MAFLD); obesity; sex dimorphism; time‐restricted feeding (TRF)

DOI:  https://doi.org/10.1113/JP287681
J Biomed Sci. 2025 Aug 19. 32(1): 77

Activation of mitophagy and proteasomal degradation confers resistance to developmental defects in postnatal skeletal muscle.

Fasih A Rahman, Mackenzie Q Graham, Alex Truong, Joe Quadrilatero.

   BACKGROUND: Postnatal skeletal muscle development leads to increased muscle mass, strength, and mitochondrial function, but the role of mitochondrial remodeling during this period is unclear. This study investigates mitochondrial remodeling during postnatal muscle development and examines how constitutive autophagy deficiency impacts these processes.
METHODS: We initially performed a broad RNA-Seq analysis using a publicly available GEO database of skeletal muscle from postnatal day 7 (P7) to postnatal day 112 (P112) to identify differentially expressed genes. This was followed by investigation of postnatal skeletal muscle development using the mitophagy report mouse line (mt-Kiema mice), as well as conditional skeletal muscle knockout (Atg7f/f:Acta1-Cre) mice.
RESULTS: Our study observed rapid growth of body and skeletal muscle mass, along with increased fiber cross-sectional area and grip strength. Mitochondrial maturation was indicated by enhanced maximal respiration, reduced electron leak, and elevated mitophagic flux, as well as increased mitochondrial localization of autophagy and mitophagy proteins. Anabolic signaling was also upregulated, coinciding with increased mitophagy and fusion signaling, and decreased biogenesis signaling. Despite the loss of mitophagic flux in skeletal muscle-specific Atg7 knockout mice, there were no changes in body or skeletal muscle mass; however, hypertrophy was observed in type IIX fibers. This lack of Atg7 and loss of mitophagy was associated with the activation of mitochondrial apoptotic signaling as well as ubiquitin-proteasome signaling, suggesting a shift in degradation mechanisms. Inhibition of the ubiquitin-proteasome system (UPS) in autophagy-deficient skeletal muscle led to significant atrophy, increased reactive oxygen species production, and mitochondrial apoptotic signaling.
CONCLUSION: These results highlight the role of mitophagy in postnatal skeletal muscle development and suggest that autophagy-deficiency triggers compensatory degradative pathways (i.e., UPS) to prevent mitochondrial apoptotic signaling and thus preserve skeletal muscle integrity in developing mice.

Keywords:  Apoptosis; Autophagy; BNIP3; Development; Mitochondria; Mitophagy; Skeletal muscle; UPS

DOI:  https://doi.org/10.1186/s12929-025-01153-7