bims-kimdis Biomed News
on Ketones, inflammation and mitochondria in disease
Issue of 2025–04–13
eighteen papers selected by
Matías Javier Monsalves Álvarez, Universidad Andrés Bello
  1. Ketone Bodies in Renal Function and Diabetic Kidney Disease.
  2. Exploring physiological beta-hydroxybutyrate level in children treated with the classical ketogenic diet for drug-resistant epilepsy.
  3. Symptoms during initiation of a ketogenic diet: a scoping review of occurrence rates, mechanisms and relief strategies.
  4. Alterations of Fat and Ketone Body Metabolism in ALS and SMA-A Prospective Observational Study.
  5. Association between ketogenic diets and depression: A cross-sectional analysis of the NHANES 2005-2023 August.
  6. Ketogenic diet attenuates neuroinflammation and restores hippocampal neurogenesis to improve CUMS induced depression-like behavior in mice.
  7. β-hydroxybutyrate serves as a regulator in ketone body metabolism through lysine β-hydroxybutyrylation.
  8. Potential inflammatory mechanisms of the ketogenic diet against febrile infection-related epilepsy syndrome.
  9. Short-term disuse shapes the adaptive response to resistance training.
  10. Metabolic effects of 3-hydroxybutyrate infusion in individuals with type 1 diabetes compared with healthy control participants: a randomised crossover trial showing intact feedback suppression of lipolysis.
  11. Balancing benefits and risks of aerobic exercise for aging and musculoskeletal health.
  12. 31P-MRS-Measured Phosphocreatine Recovery Kinetics in Human Muscles in Health and Disease-A Systematic Review and Meta-Analysis.
  13. Mitochondrial dynamics at the intersection of macrophage polarization and metabolism.
  14. The emerging role of exercise preconditioning in preventing skeletal muscle atrophy.
  15. Mitochondria and cell death signalling.
  16. Losing weight through better sleep.
  17. Revisiting insulin-stimulated hydrogen peroxide dynamics reveals a cytosolic reductive shift in skeletal muscle.
  18. Transplantation of exogenous mitochondria mitigates myocardial dysfunction after cardiac arrest.
  1. J Nutr Biochem. 2025 Apr 03. pii: S0955-2863(25)00078-6. [Epub ahead of print] 109915
    Ketone Bodies in Renal Function and Diabetic Kidney Disease.
    Hamza Mechchate.
      Diabetes, as a leading cause of chronic kidney disease (CKD) and diabetic kidney disease (DKD), underscores a significant concern, especially due to its association with health decline and mortality. In this context, the roles of ketone bodies, especially beta-hydroxybutyrate are increasingly recognized for their impact in renal physiology and the pathology of DKD. Moving beyond their conventional perception as metabolic by products, ketone bodies have been found to play a crucial role in renal health, particularly under the stresses of diabetic conditions. Serving as alternative energy sources during periods of glucose scarcity, they also function as important signaling molecules. These ketones significantly influence oxidative stress, nutrient-sensing pathways, and mitochondrial function within the kidneys. The adaptability of renal cells to utilize ketone bodies in diabetes highlights a dynamic metabolic interplay, essential for understanding renal health. The exploration of ketone body metabolism modulation, particularly through interventions like SGLT2 inhibitors and ketogenic diets, opens new avenues in managing DKD. Such insights pave the way for rethinking the role of ketone bodies in renal pathology and diabetes, pointing to novel research directions and therapeutic potentials.
    Keywords:  Diabetic nephropathy; Ketone bodies; Kidney disease; Kidney metabolism
    DOI:  https://doi.org/10.1016/j.jnutbio.2025.109915
  2. Acta Epileptol. 2025 Feb 07. 7(1): 10
    Exploring physiological beta-hydroxybutyrate level in children treated with the classical ketogenic diet for drug-resistant epilepsy.
    Xiaoying Qiao, Zimeng Ye, Jialun Wen, Sufang Lin, Dezhi Cao, Li Chen, Dongfang Zou, Huafang Zou, Man Zhang, Zhibin Chen, Patrick Kwan, Ingrid E Scheffer, Jiong Qin, Jianxiang Liao.
       BACKGROUND: The ketogenic diet (KD) therapy is a primary treatment for drug-resistant epilepsy, and beta-hydroxybutyrate (BHB) is the main ketone produced during KD. However, the pattern of increase in BHB levels is not well understood, and the reference range for BHB need to be defined. The aim of this study was to evaluate the BHB levels in the first three months, especially one week, after KD initiation, and to explore the physiological reference range for BHB.
    METHODS: In our study, a fasting initiation strategy was used for the majority of patients (252/300, 84%) who underwent fasting for 24-48 h, the rest fasted for at least 12 h. The concentration of blood BHB was measured four times a day during the first week, at one month and three months. Seizure frequency was recorded at one week, one month and three months. Responders were defined as those with a seizure reduction 50% or more compared to baseline. BHB levels were compared between responders and non-responders. The BHB levels of responders were used to calculate the reference range.
    RESULTS: A total of 300 patients were recruited, of whom 172 (57%) had accessible BHB data. BHB levels rapidly rose to 2.0 mmol/L at 19 h, peaked at 4.2 mmol/L at 43 h of therapy, and stabilized by three months. The reference range for BHB was 1.1 to 4.9 mmol/L.
    CONCLUSIONS: BHB levels increased rapidly following fasting, reaching the peak at day 2, stabilizing from the end of the first week through three months. The lower reference limit for BHB to ensure KD efficacy should be set at 1.1 mmol/L.
    Keywords:  Beta-hydroxybutyrate; Children; Epilepsy; Ketogenic diet; Reference range
    DOI:  https://doi.org/10.1186/s42494-024-00199-8
  3. Front Nutr. 2025 ;12 1538266
    Symptoms during initiation of a ketogenic diet: a scoping review of occurrence rates, mechanisms and relief strategies.
    Oddbjørn Skartun, Callum Rhys Smith, Johnny Laupsa-Borge, Simon Nitter Dankel.
       Background: Evidence for the clinical utility of ketogenic diets (KD) is mounting. The transition to a KD (keto-induction) can however trigger unpleasant transient symptoms (≪keto-flu≫) which may deter continued adherence. Knowledge of strategies that mitigate symptoms during keto-induction may facilitate adoption of a KD.
    Aim: We aimed to perform a scoping review of the available scientific literature with regards to symptom occurrence rates, possible mechanisms and proposed interventions for symptom relief during keto-induction.
    Methods: Embase, Medline and Web of Science electronic databases were searched systematically using terms associated with the KD and keto-induction in conjunction with terms capturing adverse effects. In addition, additional relevant studies were retrieved from the identified articles' references.
    Results: The available literature on keto-induction symptoms is highly heterogenous, but common transient symptoms are reported across multiple populations, including descriptions of "keto-flu," nausea, emesis, reduced appetite, hypoglycaemia, acidosis, increased risk of kidney stones, altered liver biochemistry, and skin rash. Mechanisms have been proposed based on general insights into physiology, but few have been empirically tested. However, approaches to reduce symptoms of keto-initiation are reported, including avoidance of the traditionally used fasted initiation and supplementation of medium-chain triglycerides (MCT) and ketone salts. There is a physiological rationale for supplementation with electrolytes and ketone esters, but a lack of clinical studies documenting their effect.
    Conclusion: Several transient symptoms have been associated with keto-induction, although a limited number of studies have directly examined them, or the mechanisms and possible interventions for symptom alleviation. Further research is warranted to close knowledge gaps highlighted in this review.
    Keywords:  keto flu; keto-induction; ketogenesis; ketogenic diet; side-effects; symptoms
    DOI:  https://doi.org/10.3389/fnut.2025.1538266
  4. Eur J Neurol. 2025 Apr;32(4): e70132
    Alterations of Fat and Ketone Body Metabolism in ALS and SMA-A Prospective Observational Study.
    C Herrmann, Z Uzelac, S Michels, A Weber, L Richter, Z Elmas, L Jagodzinski, C Wurster, J Schuster, J Dreyhaupt, J Dorst.
       BACKGROUND: Amyotrophic lateral sclerdosis (ALS) and spinal muscular atrophy (SMA) are motor neuron diseases associated with distinct metabolic alterations. ALS patients feature an increased resting energy expenditure (REE) causing weight loss and cachexia. In SMA, a disturbed utilization of free fatty acids has been described. These metabolic alterations negatively affect prognosis in both diseases. The objective of this study was to further characterize these changes to identify potential therapeutic targets.
    METHODS: Between 11/2020 and 08/2022, 112 ALS patients, 77 SMA patients, and 50 controls were recruited in the Department of Neurology of Ulm University. Standardized blood and urinary samples were collected to analyze fat and ketone metabolism.
    RESULTS: Ketone body levels were higher in ALS and SMA compared to controls. In both diseases, patients with higher BMI featured higher ketone bodies and free fatty acids compared to those with lower BMI, while in controls we found the opposite phenomenon. In SMA, more severe disease types were associated with higher ketone body levels. Compared to ALS, SMA patients featured higher ketone body and free fatty acid levels.
    CONCLUSIONS: Our data suggest that already during early disease stages, ALS patients produce ketone bodies to compensate for the energy deficit. In SMA, on the other hand, the persistence of ketogenesis may indicate an upregulation of all available metabolic pathways for energy production due to the disturbance of fatty acid utilization. Therefore, the application of additional sources of energy, such as ketone bodies, might constitute a promising therapeutic option in both diseases.
    Keywords:  amyotrophic lateral sclerosis; fatty acids; ketone bodies; metabolic alterations; spinal muscular atrophy
    DOI:  https://doi.org/10.1111/ene.70132
  5. J Affect Disord. 2025 Apr 05. pii: S0165-0327(25)00596-8. [Epub ahead of print]381 260-269
    Association between ketogenic diets and depression: A cross-sectional analysis of the NHANES 2005-2023 August.
    Hao Ren, Zhihao Wang, Yunbo Yuan, Yuze He, Wenhao Li, Yuhang Ou, Shuxin Zhang, Siliang Chen, Junhong Li, Yunhui Zeng, Yanhui Liu.
       BACKGROUND: The ketogenic diet (KD) is widely used for epilepsy and neurodegenerative diseases. Glutamate, the excitatory neurotransmitter in the body, has been found to be significantly elevated in the brains of some patients with depression. Ketone bodies, the main products of KD, may negatively regulate the metabolic activity of glutamate, which suggests a potential role in the onset and progression of depression. However, the relationship between KD and depression risk remains uncertain.
    METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and August 2023 to investigate the association between the ketogenic diet ratio (KDR) and depression risk. Multiple logistic regression analysis was employed to examine this association, whereas nonlinear relationships were assessed using restricted cubic splines. Stratification analysis was employed to examine the association between KDR and depression severity. Subgroup analyses were also performed.
    RESULTS: In a fully adjusted model accounting for confounding variables, KDR was significantly associated with depression risk. Two-piecewise linear regression analysis better fitted the association (KDR < 0.35, OR: 0.11; 95%CI: 0.03-0.35; P < 0.001). Subgroup analyses indicated that this association between KDR and depression was particularly pronounced in certain specific populations. We further observed a significant correlation between KDR and depression severity (P < 0.001).
    CONCLUSION: Higher KDR was associated with a reduced risk of depression, with potentially greater efficacy observed in specific populations. Additionally, KDR has been found to be significantly associated with the severity of depression. Further study could investigate their potential mechanism.
    Keywords:  Depression; Ketogenic diet; Ketogenic diet ratio; NHANES
    DOI:  https://doi.org/10.1016/j.jad.2025.04.035
  6. Food Funct. 2025 Apr 08.
    Ketogenic diet attenuates neuroinflammation and restores hippocampal neurogenesis to improve CUMS induced depression-like behavior in mice.
    Jinyuan Liang, Jingxi Zhang, Jingyu Sun, Qingsheng Liang, Yingtong Zhan, Zhiyou Yang, Yongping Zhang, Leigang Jin, Chuanyin Hu, Yun-Tao Zhao.
      The ketogenic diet (KD) has been proposed as a potential treatment for depression. However, the underlying mechanisms remain poorly understood. This study aimed to evaluate further the effects of KD on chronic unpredictable mild stress (CUMS)-induced depression in mice and investigate the underlying mechanisms. The results demonstrated that KD intervention significantly alleviated CUMS-induced depression-like behaviors, as evidenced by a decrease in immobility time in the forced swimming test and tail suspension test, an increase in distance traveled in the open field test, and a greater preference for sucrose in the sucrose preference test. KD alleviated neuroinflammation by reducing the levels of glial cell activation markers Iba-1 and GFAP, inhibiting the expression of inflammatory factors IL-1β, TNF-α, and COX-2, and suppressing the overactivation of the TLR4/MyD88/NF-κB signaling pathway. Furthermore, KD increased the number of DCX-, BrdU-, and PSD95-positive cells in the hippocampus and enhanced the BDNF/TrkB/CREB and Wnt/β-catenin signaling pathways, thereby promoting hippocampal neurogenesis. These findings suggested that KD alleviated CUMS-induced depression-like behaviors in mice by reducing neuroinflammation, enhancing neurotrophic signaling, and promoting hippocampal neurogenesis, thereby providing a mechanistic basis for its potential as a novel dietary antidepressant therapy.
    DOI:  https://doi.org/10.1039/d5fo00226e
  7. J Biol Chem. 2025 Apr 02. pii: S0021-9258(25)00324-2. [Epub ahead of print] 108475
    β-hydroxybutyrate serves as a regulator in ketone body metabolism through lysine β-hydroxybutyrylation.
    Jie Fang, Zhenghui Hu, Ting Luo, Shiyin Chen, Jie Li, Huaping Yang, Xia Sheng, Xinji Zhang, Ziyu Zhang, Caifeng Xie.
      β-hydroxybutyrate (β-HB) may serve as a signaling metabolite in many physiological processes beyond a fuel source for tissues. However, whether and how it is involved in ketone body metabolism is still unknown. The present study aims to investigate the role of lysine β-hydroxybutyrylation (Kbhb) modification mediated by β-HB in regulating ketone body metabolic homeostasis both in vivo and in vitro. The starvation ketosis and type 1 diabetes mouse models were introduced to evaluate the influence of β-HB on Kbhb modification in mice. The lysine β-hydroxybutyrylation modifications of OXCT1 and HMGCS2, two rate-limiting enzymes involved in ketogenesis and utilization, showed a positive correlation with the level of β-HB both in vitro and in vivo. The modification levels of the enzymes increased during fasting but decreased after refeeding. However, the Kbhb modification level in all detected tissues showed minor change since the blood ketone body increased non-significantly in the type 1 diabetes mouse model. The in vitro experiments further indicated that mutation at the Kbhb modification site significantly inhibited the enzymatic activity of OXCT1 but not HMGCS2. SIRT1 and CBP were identified both in vitro and in vivo as potential Kbhb dehydrogenase and transferase for OXCT1, respectively. Lysine β-hydroxybutyrylation modification at lysine 421 of OXCT1 increases its enzyme activity during β-HB accumulation, accelerating the utilization of the ketone body and finally maintaining metabolism homeostasis. Our present study proposes a new ketone body metabolic regulatory mode primarily mediated by lysine β-hydroxybutyrylation modifications of OXCT1 during β-HB accumulation.
    Keywords:  HMGCS2; Ketone body; OXCT1; β-HB; β-hydroxybutyrylation
    DOI:  https://doi.org/10.1016/j.jbc.2025.108475
  8. Acta Epileptol. 2025 Jan 10. 7(1): 3
    Potential inflammatory mechanisms of the ketogenic diet against febrile infection-related epilepsy syndrome.
    Juan Wang, Lingling Xie, Li Jiang.
      Febrile infection-related epilepsy syndrome (FIRES) is a rare epilepsy syndrome with unclear pathogenesis, characterized by fever-induced, super-refractory status epilepticus and high mortality. Studies have shown that ketogenic diet (KD) is effective in controlling convulsions in FIRES, but its mechanisms are unclear. This paper intends to summarize the mechanisms by which KD may exert effects against FIRES. Clinical studies have shown that patients with FIRES have elevated levels of various inflammatory factors such as interleukin (IL)-6, IL-8, IL-10, and so on. KD may exert anti-FIRES effects through several potential inflammatory pathways, including nuclear factor -κB (NF-κB) and NLR family pyrin domain containing 3 (NLRP3). Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) network suggested that KD may play an anti-inflammatory role through several pathways such as cellular senescence and neutrophil extracellular trap formation. These mechanisms need to be further investigated.
    Keywords:  Febrile infection-related epilepsy syndrome; Inflammation; Ketogenic diet; Mechanisms
    DOI:  https://doi.org/10.1186/s42494-024-00187-y
  9. J Physiol. 2025 Apr 08.
    Short-term disuse shapes the adaptive response to resistance training.
    Jacob Andresen.
      
    Keywords:  exercise physiology; muscle adaptation; muscle physiology; muscle plasticity; resistance training
    DOI:  https://doi.org/10.1113/JP288530
  10. Diabetologia. 2025 Apr 10.
    Metabolic effects of 3-hydroxybutyrate infusion in individuals with type 1 diabetes compared with healthy control participants: a randomised crossover trial showing intact feedback suppression of lipolysis.
    Maj Bangshaab, Mads V Svart, Nikolaj Rittig, Mette G B Pedersen, Jens Voigt, Niels Jessen, Niels Møller.
       AIMS/HYPOTHESIS: Diabetic ketoacidosis remains a severe complication in type 1 diabetes, arising from insufficient insulin levels and accelerated lipolytic rate, leading to increased β-oxidation of NEFA and ketone body production in the liver. The ketone body 3-hydroxybutyrate (3-OHB) inhibits lipolysis in healthy individuals. The current study aimed to test whether this feedback suppression of lipolysis by 3-OHB is disrupted in individuals with type 1 diabetes.
    METHODS: We used a single-blind, randomised, crossover design to study ten men diagnosed with type 1 diabetes and ten healthy control participants. Eligibility criteria were male sex, age ≥18 years, BMI of 19-26 kg/m2 and no severe comorbidities/diseases. Following an overnight fast, each participant received two 3 h i.v. infusions: (i) sodium-D/L-3-OHB and (ii) iso-osmolar saline (NaCl), separated by a 1 h washout period. The order of the two interventions was assigned by randomisation for each participant. Participants were blinded to the allocation throughout the study day, but investigators were aware of the assigned intervention order. We evaluated the lipolytic rate and glucose turnover using [9,10-3H]palmitate and [3-3H]glucose tracers. Additionally, adipose tissue signalling was quantified using western blotting techniques in subcutaneous abdominal adipose tissue biopsies. The primary endpoint measure was palmitate flux (lipolytic rate).
    RESULTS: During the infusion of 3-OHB, the D/L-3-OHB blood concentrations increased to 3.3 ± 0.7 mmol/l in participants with type 1 diabetes compared with 2.9 ± 0.5 mmol/l in control participants (p=0.03). The infusion effectively suppressed the lipolytic rates by more than 50% (p<0.001) and reduced circulating NEFA by approximately 0.5 mmol/l (p<0.001) compared with NaCl in both participants with type 1 diabetes and control participants. In adipose tissue, 3-OHB reduced protein kinase A phosphorylation of perilipin (p<0.001) and hormone-sensitive lipase phosphorylation at Ser660 (p<0.001) and Ser563 (p<0.01) similarly in participants with type 1 diabetes and control participants. Indices of glucose metabolism remained unaffected throughout in both groups.
    CONCLUSIONS/INTERPRETATION: Our findings indicate that, in individuals with type 1 diabetes, the suppression of lipolysis, blood NEFA concentrations and adipose tissue signalling activity in response to 3-OHB remains intact compared with healthy control participants. These findings imply that derailment of receptor signalling by 3-OHB is unlikely to be involved in the development of diabetic ketoacidosis.
    TRIAL REGISTRATION: ClinicalTrials.gov NCT04656236 FUNDING: Open access funding provided by Aarhus Universitet. This study was supported by the Novo Nordisk Foundation (NNF19OC0058872) and the Health Research Foundation of Central Denmark Region.
    Keywords:  3-Hydroxybutyrate; Adipose tissue signalling; Insulin resistance; Ketoacidosis; Ketones; Lipolysis; Metabolism; Type 1 diabetes
    DOI:  https://doi.org/10.1007/s00125-025-06423-5
  11. Exp Gerontol. 2025 Apr 02. pii: S0531-5565(25)00076-2. [Epub ahead of print] 112747
    Balancing benefits and risks of aerobic exercise for aging and musculoskeletal health.
    Wenduo Liu, Zilin Wang, Yu Gu, Jae Cheol Kim, Sang Hyun Kim.
       BACKGROUND: Long-term exercise is recognized as one of the most effective means of maintaining health after aging, but the relationship between moderate exercise and health in the older population is often overlooked.
    OBJECTIVE: The present study was conducted to investigate the effects of excessive endurance exercise on the old mice musculoskeletal system.
    RESULTS: The 8 weeks of normal endurance exercise significantly improved skeletal muscle mitochondrial biogenesis and increased femoral osteogenesis in young and old mice. However, the continued accumulation of total exercise volume as the exercise cycle was prolonged resulted in the younger and older mice exhibiting different exercise effects. After 8-16 weeks of moderate-intensity endurance exercise, young mice showed consistent effects of increased mitochondrial biogenesis in skeletal muscle. However, after 12-16 weeks of moderate-intensity endurance exercise, the original effects of exercise-induced mitochondrial biosynthesis were instead impaired in older mice. After 16 weeks of exercise, the aged mice showed a produces consumptive weight loss, an increase inflammation level in adipose tissue, and a decrease in femoral bone mineral density. Interestingly, with an increase in total exercise, the level of skeletal muscle inflammation in old mice did not increase significantly, while a longer exercise cycle reduced the level of skeletal muscle apoptosis, thereby maintaining the state of skeletal muscle.
    CONCLUSIONS: Appropriate moderate-intensity endurance exercise has a significant gain in maintaining musculoskeletal health in aged mice. However, excessive endurance impairs the health of the musculoskeletal system in aged mice.
    Keywords:  Age-related adaptation; Inflammation; Mitochondria; Moderate-intensity aerobic exercise; Musculoskeletal health
    DOI:  https://doi.org/10.1016/j.exger.2025.112747
  12. NMR Biomed. 2025 May;38(5): e70023
    31P-MRS-Measured Phosphocreatine Recovery Kinetics in Human Muscles in Health and Disease-A Systematic Review and Meta-Analysis.
    Maninder Singh, Aditya Jhajharia, Rajat Pruthi, Owen T Carmichael.
      The noninvasive, in vivo measurement of postexercise phosphocreatine (PCr) recovery kinetics using 31-phosphorus magnetic resonance spectroscopy (31P-MRS) is a highly prevalent method for assessing skeletal muscle energetics. However, 31P-MRS methodology is notoriously laboratory-specific, leading to uncertainty about the normal range of PCr recovery kinetics among healthy individuals, as well as relationships with disease and demographic factors. This systematic review and meta-analysis characterized the normal range of PCr recovery kinetics from 31P-MRS in human skeletal muscles across the lifespan, differences between healthy and those with muscle-related diseases, and relationships between intermuscular PCr recovery measurements and demographic factors. PubMed, Web of Science, Cochrane, and Google Scholar databases were searched for PCr recovery studies, which resulted in a final set of 128 studies eligible for meta-analysis. Studies were categorized into three muscle groups (forearm, upper leg, and lower leg) and further subdivided into three groups: diseased, control (the comparator group in studies of disease), and healthy (those recruited into studies that lacked a disease group). Only English-language studies were included. All statistical analysis was performed using Stata 17 software. Forest plots showed significant heterogeneity across PCr recovery time estimates and outlier study removal significantly reduced this heterogeneity. Greater age was associated with longer PCr recovery in upper leg muscles among both healthy (ρ = 0.387, p < 0.05) and diseased (ρ = 0.733, p < 0.05) individuals. Additionally, longer PCr recovery time was correlated with more acidic end-of-exercise pH in all three muscle groups among healthy individuals. In conclusion, skeletal muscle energetics as indexed by 31P-MRS-based PCr recovery time is similar across three different skeletal muscle groups among healthy people. Common diseases significantly prolong PCr recovery times. Methodological heterogeneity has a significant impact on PCr recovery time measurements in this literature. Greater age and more acidic pH increase PCr recovery time among healthy people.
    DOI:  https://doi.org/10.1002/nbm.70023
  13. Front Immunol. 2025 ;16 1520814
    Mitochondrial dynamics at the intersection of macrophage polarization and metabolism.
    Pan Li, Zhengbo Fan, Yanlan Huang, Liang Luo, Xiaoyan Wu.
      Macrophages are vital sentinels in innate immunity, and their functions cannot be performed without internal metabolic reprogramming. Mitochondrial dynamics, especially mitochondrial fusion and fission, contributes to the maintenance of mitochondrial homeostasis. The link between mitochondrial dynamics and macrophages in the past has focused on the immune function of macrophages. We innovatively summarize and propose a link between mitochondrial dynamics and macrophage metabolism. Among them, fusion-related FAM73b, MTCH2, SLP-2 (Stomatin-like protein 2), and mtSIRT, and fission-related Fis1 and MTP18 may be the link between mitochondrial dynamics and macrophage metabolism association. Furthermore, post-translational modifications (PTMs) of mtSIRT play prominent roles in mitochondrial dynamics-macrophage metabolism connection, such as deacetylates and hypersuccinylation. MicroRNAs such as miR-150, miR-15b, and miR-125b are also possible entry points. The metabolic reprogramming of macrophages through the regulation of mitochondrial dynamics helps improve their adaptability and resistance to adverse environments and provides therapeutic possibilities for various diseases.
    Keywords:  fission; fusion; macrophage; metabolism; mitochondrial dynamics
    DOI:  https://doi.org/10.3389/fimmu.2025.1520814
  14. Front Physiol. 2025 ;16 1559594
    The emerging role of exercise preconditioning in preventing skeletal muscle atrophy.
    Xu Zhou, Shiming Li, Lu Wang, Jun Wang, Peng Zhang, Xiaoping Chen.
      Skeletal muscle atrophy, characterized by the loss of muscle mass and function, can result from disuse, aging, disease, drug. Exercise preconditioning-a form of exercise training performed before these harmful threats-induces notable remodeling and extensive biochemical adaptations in skeletal muscle, creating a protective phenotype in muscle fibers, and thus serving as an effective intervention for preventing skeletal muscle atrophy. Here, we review the current understanding relating to how exercise preconditioning protects skeletal muscle from damage caused by inactivity, sarcopenia, disease, or pharmacological intervention, with an emphasis on the cellular mechanisms involved. Key mechanisms highlighted as making a significant contribution to the protective effects of exercise on skeletal muscle fibers include mitochondria; the expression of cytoprotective proteins such as HSP72, SOD2, SESN2, PGC-1α and AMPK; and the regulation of oxidative stress. These findings underscore the potential of exercise preconditioning as a non-pharmacological intervention for preserving muscle mass and function, as well as preventing muscular atrophy, ultimately improving the quality of life for at-risk populations.
    Keywords:  disuse atrophy; exercise preconditioning; mitochondrial dysfunction; muscular atrophy; sarcopenia
    DOI:  https://doi.org/10.3389/fphys.2025.1559594
  15. Curr Opin Cell Biol. 2025 Apr 10. pii: S0955-0674(25)00048-1. [Epub ahead of print]94 102510
    Mitochondria and cell death signalling.
    Ella Hall-Younger, Stephen Wg Tait.
      Mitochondria are essential organelles in the life and death of a cell. During apoptosis, mitochondrial outer membrane permeabilisation (MOMP) engages caspase activation and cell death. Under nonlethal apoptotic stress, some mitochondria undergo permeabilisation, termed minority MOMP. Nonlethal apoptotic signalling impacts processes including genome stability, senescence and innate immunity. Recent studies have shown that upon MOMP, mitochondria and consequent signalling can trigger inflammation. We discuss how this occurs, and how mitochondrial inflammation might be targeted to increase tumour immunogenicity. Finally, we highlight how mitochondria contribute to other types of cell death including pyroptosis and ferroptosis. Collectively, these studies reveal critical new insights into how mitochondria regulate cell death, highlighting that mitochondrial signals engaged under nonlethal apoptotic stress have wide-ranging biological functions.
    DOI:  https://doi.org/10.1016/j.ceb.2025.102510
  16. Nature. 2025 Apr 09.
    Losing weight through better sleep.
    Tammy Worth.
      
    Keywords:  Metabolism; Neuroscience; Obesity; Physiology
    DOI:  https://doi.org/10.1038/d41586-025-00998-0
  17. Redox Biol. 2025 Mar 25. pii: S2213-2317(25)00120-X. [Epub ahead of print]82 103607
    Revisiting insulin-stimulated hydrogen peroxide dynamics reveals a cytosolic reductive shift in skeletal muscle.
    Carlos Henríquez-Olguín, Samantha Gallero, Anita Reddy, Kaspar W Persson, Farina L Schlabs, Christian T Voldstedlund, Gintare Valentinaviciute, Roberto Meneses-Valdés, Casper M Sigvardsen, Bente Kiens, Edward T Chouchani, Erik A Richter, Thomas E Jensen.
      The intracellular redox state is crucial for insulin responses in peripheral tissues. Despite the longstanding belief that insulin signaling increases hydrogen peroxide (H2O2) production leading to reversible oxidation of cysteine thiols, evidence is inconsistent and rarely involves human tissues. In this study, we systematically investigated insulin-dependent changes in subcellular H2O2 levels and reversible cysteine modifications across mouse and human skeletal muscle models. Utilizing advanced redox tools-including genetically encoded H2O2 sensors and non-reducing immunoblotting-we consistently observed no increase in subcellular H2O2 levels following insulin stimulation. Instead, stoichiometric cysteine proteome analyses revealed a selective pro-reductive shift in cysteine modifications affecting insulin transduction related proteins, including Cys179 on GSK3β and Cys416 on Ras and Rab Interactor 2 (RIN2). Our findings challenge the prevailing notion that insulin promotes H2O2 generation in skeletal muscle and suggest that an insulin-stimulated pro-reductive shift modulates certain aspects of insulin signal transduction.
    DOI:  https://doi.org/10.1016/j.redox.2025.103607
  18. Elife. 2025 Apr 10. pii: RP98554. [Epub ahead of print]13
    Transplantation of exogenous mitochondria mitigates myocardial dysfunction after cardiac arrest.
    Zhen Wang, Jie Zhu, Mengda Xu, Xuyuan Ma, Maozheng Shen, Jingyu Yan, Guosheng Gan, Xiang Zhou.
      The incidence of post-cardiac arrest myocardial dysfunction (PAMD) is high, and there is currently no effective treatment available. This study aims to investigate the protective effects of exogenous mitochondrial transplantation in Sprague-Dawley (SD) rats. Exogenous mitochondrial transplantation can enhance myocardial function and improve the survival rate. Mechanistic studies suggest that mitochondrial transplantation can limit impairment in mitochondrial morphology, augment the activity of mitochondrial complexes II and IV, and raise ATP level. As well, mitochondrial therapy ameliorated oxidative stress imbalance, reduced myocardial injury, and thus improved PAMD after cardiopulmonary resuscitation (CPR).
    Keywords:  apoptosis; medicine; mitochondria; muscle fiber; rat
    DOI:  https://doi.org/10.7554/eLife.98554
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