bims-kimdis Biomed News
on Ketones, inflammation and mitochondria in disease
Issue of 2022–09–25
eightteen papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins
  1. Inflammation: Roles in Skeletal Muscle Atrophy.
  2. 2-month ketogenic diet preferentially alters skeletal muscle and augments cognitive function in middle aged female mice.
  3. Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.
  4. Ketogenic Diets and Mitochondrial Function: Benefits for Aging but not for Athletes.
  5. Effects of Ketogenic Diet on Muscle Metabolism in Health and Disease.
  6. The impact of diet upon mitochondrial physiology (Review).
  7. Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor.
  8. Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.
  9. Aerobic Exercise Prevents Chronic Inflammation and Insulin Resistance in Skeletal Muscle of High-Fat Diet Mice.
  10. How location and cellular signaling combine to activate the NLRP3 inflammasome.
  11. Excitation-contraction coupling in mammalian skeletal muscle: Blending old and last-decade research.
  12. Ketogenic diet attenuates post-cardiac arrest brain injury by upregulation of pentose phosphate pathway-mediated antioxidant defense in a mouse model of cardiac arrest.
  13. The Effects of Concurrent Training Combined with Low-Carbohydrate High-Fat Ketogenic Diet on Body Composition and Aerobic Performance: A Systematic Review and Meta-Analysis.
  14. Increased Efficiency of Mitochondrial Coupling with a Reduction in Other Mitochondrial Respiratory Parameters in Peripheral Blood Mononuclear Cells is Observed in Older Adults.
  15. Is Intermittent Fasting Better Than Continuous Energy Restriction for Adults with Overweight and Obesity?
  16. Iron Supplementation Improves Skeletal Muscle Contractile Properties in Mice with CKD.
  17. The Effect of Uridine on the State of Skeletal Muscles and the Functioning of Mitochondria in Duchenne Dystrophy.
  18. NLRP3 inflammasome: A potential therapeutic target to minimize renal ischemia/reperfusion injury during transplantation.
  1. Antioxidants (Basel). 2022 Aug 29. pii: 1686. [Epub ahead of print]11(9):
    Inflammation: Roles in Skeletal Muscle Atrophy.
    Yanan Ji, Ming Li, Mengyuan Chang, Ruiqi Liu, Jiayi Qiu, Kexin Wang, Chunyan Deng, Yuntian Shen, Jianwei Zhu, Wei Wang, Lingchi Xu, Hualin Sun.
      Various diseases can cause skeletal muscle atrophy, usually accompanied by inflammation, mitochondrial dysfunction, apoptosis, decreased protein synthesis, and enhanced proteolysis. The underlying mechanism of inflammation in skeletal muscle atrophy is extremely complex and has not been fully elucidated, thus hindering the development of effective therapeutic drugs and preventive measures for skeletal muscle atrophy. In this review, we elaborate on protein degradation pathways, including the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), the calpain and caspase pathways, the insulin growth factor 1/Akt protein synthesis pathway, myostatin, and muscle satellite cells, in the process of muscle atrophy. Under an inflammatory environment, various pro-inflammatory cytokines directly act on nuclear factor-κB, p38MAPK, and JAK/STAT pathways through the corresponding receptors, and then are involved in muscle atrophy. Inflammation can also indirectly trigger skeletal muscle atrophy by changing the metabolic state of other tissues or cells. This paper explores the changes in the hypothalamic-pituitary-adrenal axis and fat metabolism under inflammatory conditions as well as their effects on skeletal muscle. Moreover, this paper also reviews various signaling pathways related to muscle atrophy under inflammatory conditions, such as cachexia, sepsis, type 2 diabetes mellitus, obesity, chronic obstructive pulmonary disease, chronic kidney disease, and nerve injury. Finally, this paper summarizes anti-amyotrophic drugs and their therapeutic targets for inflammation in recent years. Overall, inflammation is a key factor causing skeletal muscle atrophy, and anti-inflammation might be an effective strategy for the treatment of skeletal muscle atrophy. Various inflammatory factors and their downstream pathways are considered promising targets for the treatment and prevention of skeletal muscle atrophy.
    Keywords:  ALP; UPS; inflammation; skeletal muscle atrophy
    DOI:  https://doi.org/10.3390/antiox11091686
  2. Aging Cell. 2022 Sep 23. e13706
    2-month ketogenic diet preferentially alters skeletal muscle and augments cognitive function in middle aged female mice.
    Suraj J Pathak, Zeyu Zhou, Danielle Steffen, Tommy Tran, Yael Ad, Jon J Ramsey, Jennifer M Rutkowsky, Keith Baar.
      The effect of a ketogenic diet (KD) on middle aged female mice is poorly understood as most of this work have been conducted in young female mice or diseased models. We have previously shown that an isocaloric KD started at middle age in male mice results in enhanced mitochondrial mass and function after 2 months on diet and improved cognitive behavior after being on diet for 14 months when compared with their control diet (CD) fed counterparts. Here, we aimed to investigate the effect of an isocaloric 2-month KD or CD on healthy 14-month-old female mice. At 16 months of age cognitive behavior tests were performed and then serum, skeletal muscle, cortex, and hippocampal tissues were collected for biochemical analysis. Two months on a KD resulted in enhanced cognitive behavior associated with anxiety, memory, and willingness to explore. The improved neurocognitive function was associated with increased PGC1α protein in the gastrocnemius (GTN) muscle and nuclear fraction. The KD resulted in a tissue specific increase in mitochondrial mass and kynurenine aminotransferase (KAT) levels in the GTN and soleus muscles, with a corresponding decrease in kynurenine and increase in kynurenic acid levels in serum. With KAT proteins being responsible for converting kynurenine into kynurenic acid, which is unable to cross the blood brain barrier and be turned into quinolinic acid-a potent neurotoxin, this study provides a potential mechanism of crosstalk between muscle and brain in mice on a KD that may contribute to improved cognitive function in middle-aged female mice.
    Keywords:  Alzheimer's disease; acetylation; cognitive behavior; mitochondria; skeletal muscle
    DOI:  https://doi.org/10.1111/acel.13706
  3. J Biol Rhythms. 2022 Sep 21. 7487304221122662
    Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.
    Ryan A Martin, Karyn A Esser.
      Circadian rhythms drive our daily behaviors to coincide with the earth's rotation on an approximate 24-h cycle. The circadian clock mechanism present in nearly every cell is responsible for our circadian rhythms and is comprised of a transcriptional-translational feedback loop in mammals. The central clock resides in the hypothalamus responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from feeding and activity. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue with the ability to influence and adjust the muscle clock phase in response to exercise timing. Since the skeletal muscle clock is also involved in the expression of tissue-specific gene expression-including glucoregulatory genes-this might suggest a role for exercise timing as a therapeutic strategy in metabolic diseases, like type 2 diabetes. Notably, those with type 2 diabetes have accompanied disruptions in their skeletal muscle clock mechanism which may also be related to the increased risk of type 2 diabetes seen among shift workers. Therefore, the direct influence of exercise on the skeletal muscle clock might support the use of exercise timing to provide disease-mitigating effects. Here, we highlight the potential use of time-of-day exercise as a chronotherapeutic tool within circadian medicine to improve the metabolic profile of type 2 diabetes and support long-term glycemic control, potentially working through the skeletal muscle clock and circadian physiology.
    Keywords:  circadian rhythm; exercise; metabolism; muscle clock; skeletal muscle
    DOI:  https://doi.org/10.1177/07487304221122662
  4. Exerc Sport Sci Rev. 2022 Sep 16.
    Ketogenic Diets and Mitochondrial Function: Benefits for Aging but not for Athletes.
    Suraj J Pathak, Keith Baar.
       ABSTRACT: As humans age, we lose skeletal muscle mass, even in the absence of disease (sarcopenia), increasing the risk of death. Low mitochondrial mass and activity contributes to sarcopenia. It is our hypothesis that, a ketogenic diet improves skeletal muscle mitochondrial mass and function when they have declined due to aging or disease, but not in athletes where mitochondrial quality is high.
    DOI:  https://doi.org/10.1249/JES.0000000000000307
  5. Nutrients. 2022 Sep 16. pii: 3842. [Epub ahead of print]14(18):
    Effects of Ketogenic Diet on Muscle Metabolism in Health and Disease.
    Elmira I Yakupova, Alexey D Bocharnikov, Egor Y Plotnikov.
      Dietary intervention is widely used as a therapeutic approach ranging from the treatment of neurological disorders to attempts to extend lifespan. The most important effect of various diets is a change in energy metabolism. Since muscles constitute 40% of total body mass and are one of the major sites of glucose and energy uptake, various diets primarily affect their metabolism, causing both positive and negative changes in physiology and signaling pathways. In this review, we discuss changes in the energy metabolism of muscles under conditions of the low-carbohydrate, high-fat diet/ketogenic diet (KD), fasting, or administration of exogenous ketone bodies, which are all promising approaches to the treatment of various diseases. KD's main influence on the muscle is expressed through energy metabolism changes, particularly decreased carbohydrate and increased fat oxidation. This affects mitochondrial quantity, oxidative metabolism, antioxidant capacity, and activity of enzymes. The benefits of KD for muscles stay controversial, which could be explained by its different effects on various fiber types, including on muscle fiber-type ratio. The impacts of KD or of its mimetics are largely beneficial but could sometimes induce adverse effects such as cardiac fibrosis.
    Keywords:  fasting; heart; ketogenic diet; ketone bodies; muscle; muscle metabolism
    DOI:  https://doi.org/10.3390/nu14183842
  6. Int J Mol Med. 2022 Nov;pii: 135. [Epub ahead of print]50(5):
    The impact of diet upon mitochondrial physiology (Review).
    Ioannis D Kyriazis, Eleni Vassi, Maria Alvanou, Christos Angelakis, Zoi Skaperda, Fotios Tekos, Venkata Naga Srikanth Garikipati, Demetrios A Spandidos, Demetrios Kouretas.
      Mitochondria are considered the 'powerhouses' of cells, generating the essential energy in the form of adenosine triphosphate that they need for their energy demands. Nevertheless, their function is easily adaptable as regards the energy demands and the availability of chemical substrates. This allows cells to buffer sudden changes and reassure cellular metabolism, growth or survival. Currently, humans have different dietary habits, which provide several stimuli to the cell. According to the energy substrate availability due to the diet quality and diet temporality, mitochondrial physiology is greatly affected. The present review article aimed to collect all the available information that has been published to date concerning the impact of five different popular diets (high‑fat diet, ketogenic diet, fasting, caloric restriction diet and the Mediterranean diet) on specific mitochondrial physiological aspects, such as function, biogenesis, mitophagy and mitochondrial fission/fusion.
    Keywords:  biogenesis; caloric restriction; dynamics; fasting; high‑fat diet; ketogenic; mitochondria; mitophagy; physiology
    DOI:  https://doi.org/10.3892/ijmm.2022.5191
  7. Brain Sci. 2022 Aug 27. pii: 1143. [Epub ahead of print]12(9):
    Influence of Nutritional Ketosis Achieved through Various Methods on Plasma Concentrations of Brain Derived Neurotropic Factor.
    Madison L Kackley, Alex Buga, Chris D Crabtree, Teryn N Sapper, Craig A McElroy, Brian C Focht, William J Kraemer, Jeff S Volek.
      Brain-Derived Neurotropic Factor (BDNF) expression is decreased in conditions associated with cognitive decline as well as metabolic diseases. One potential strategy to improve metabolic health and elevate BDNF is by increasing circulating ketones. Beta-Hydroxybutyrate (BHB) stimulates BDNF expression, but the association of circulating BHB and plasma BDNF in humans has not been widely studied. Here, we present results from three studies that evaluated how various methods of inducing ketosis influenced plasma BDNF in humans. Study 1 determined BDNF responses to a single bout of high-intensity cycling after ingestion of a dose of ketone salts in a group of healthy adults who were habitually consuming either a mixed diet or a ketogenic diet. Study 2 compared how a ketogenic diet versus a mixed diet impacts BDNF levels during a 12-week resistance training program in healthy adults. Study 3 examined the effects of a controlled hypocaloric ketogenic diet, with and without daily use of a ketone-salt, on BDNF levels in overweight/obese adults. We found that (1) fasting plasma BDNF concentrations were lower in keto-adapted versus non keto-adapted individuals, (2) intense cycling exercise was a strong stimulus to rapidly increase plasma BDNF independent of ketosis, and (3) clinically significant weight loss was a strong stimulus to decrease fasting plasma BDNF independent of diet composition or level of ketosis. These results highlight the plasticity of plasma BDNF in response to lifestyle factors but does not support a strong association with temporally matched BHB concentrations.
    Keywords:  BDNF; BHB; BHB salts; exercise; ketogenic diet; weight loss
    DOI:  https://doi.org/10.3390/brainsci12091143
  8. Nutrients. 2022 Sep 17. pii: 3851. [Epub ahead of print]14(18):
    Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.
    Simone Dal Bello, Francesca Valdemarin, Deborah Martinuzzi, Francesca Filippi, Gian Luigi Gigli, Mariarosaria Valente.
      In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer.
    Keywords:  Warburg effect; cancer; glioblastoma; glioma; ketogenic diet; ketones; ketosis; tumor
    DOI:  https://doi.org/10.3390/nu14183851
  9. Nutrients. 2022 Sep 10. pii: 3730. [Epub ahead of print]14(18):
    Aerobic Exercise Prevents Chronic Inflammation and Insulin Resistance in Skeletal Muscle of High-Fat Diet Mice.
    Nan Li, Haiyan Shi, Qiaofeng Guo, Yanming Gan, Yuhang Zhang, Jiajie Jia, Liang Zhang, Yue Zhou.
      Obesity is commonly accompanied by chronic tissue inflammation and leads to insulin resistance. Aerobic exercise is an essential treatment for insulin resistance and has anti-inflammatory effects. However, the molecular mechanisms of exercise on obesity-associated inflammation and insulin resistance remain largely unknown. Here, we evaluated the effects of aerobic exercise on inflammation and insulin resistance in skeletal muscles of high-fat diet (HFD) mice. Male C57BL/6J mice were fed a high-fat diet or a normal diet for 12 weeks, and then aerobic training was performed on a treadmill for 8 weeks. Body weight, fasting blood glucose, food intake levels, and glucose and insulin tolerance were evaluated. The levels of cytokines, skeletal muscle insulin resistance, and inflammation were also analyzed. Eight weeks of aerobic exercise attenuated HFD-induced weight gain and glucose intolerance, and improved insulin sensitivity. This was accompanied by enhanced insulin signaling. Exercise directly resulted in a significant reduction of lipid content, inflammation, and macrophage infiltration in skeletal muscles. Moreover, exercise alleviated HFD-mediated inflammation by suppressing the activation of the NF-κB pathway within skeletal muscles. These results revealed that aerobic exercise could lead to an anti-inflammatory phenotype with protection from skeletal muscle insulin resistance in HFD-induced mice.
    Keywords:  NF-κB pathway; aerobic exercise; inflammation; insulin resistance; skeletal muscle
    DOI:  https://doi.org/10.3390/nu14183730
  10. Cell Mol Immunol. 2022 Sep 20.
    How location and cellular signaling combine to activate the NLRP3 inflammasome.
    Anil Akbal, Alesja Dernst, Marta Lovotti, Matthew S J Mangan, Róisín M McManus, Eicke Latz.
      NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) is a cytosolic innate immune sensor of cellular stress signals, triggered by infection and sterile inflammation. Upon detection of an activating stimulus, NLRP3 transitions from an inactive homo-oligomeric multimer into an active multimeric inflammasome, which promotes the helical oligomeric assembly of the adaptor molecule ASC. ASC oligomers provide a platform for caspase-1 activation, leading to the proteolytic cleavage and activation of proinflammatory cytokines in the IL-1 family and gasdermin D, which can induce a lytic form of cell death. Recent studies investigating both the cellular requirement for NLRP3 activation and the structure of NLRP3 have revealed the complex regulation of NLRP3 and the multiple steps involved in its activation. This review presents a perspective on the biochemical and cellular processes controlling the assembly of the NLRP3 inflammasome with particular emphasis on structural regulation and the role of organelles. We also highlight the latest research on metabolic control of this inflammatory pathway and discuss promising clinical targets for intervention.
    Keywords:  Inflammasome; Localization; Mechanism; NLRP3; Regulation; Structure
    DOI:  https://doi.org/10.1038/s41423-022-00922-w
  11. Front Physiol. 2022 ;13 989796
    Excitation-contraction coupling in mammalian skeletal muscle: Blending old and last-decade research.
    Pura Bolaños, Juan C Calderón.
      The excitation-contraction coupling (ECC) in skeletal muscle refers to the Ca2+-mediated link between the membrane excitation and the mechanical contraction. The initiation and propagation of an action potential through the membranous system of the sarcolemma and the tubular network lead to the activation of the Ca2+-release units (CRU): tightly coupled dihydropyridine and ryanodine (RyR) receptors. The RyR gating allows a rapid, massive, and highly regulated release of Ca2+ from the sarcoplasmic reticulum (SR). The release from triadic places generates a sarcomeric gradient of Ca2+ concentrations ([Ca2+]) depending on the distance of a subcellular region from the CRU. Upon release, the diffusing Ca2+ has multiple fates: binds to troponin C thus activating the contractile machinery, binds to classical sarcoplasmic Ca2+ buffers such as parvalbumin, adenosine triphosphate and, experimentally, fluorescent dyes, enters the mitochondria and the SR, or is recycled through the Na+/Ca2+ exchanger and store-operated Ca2+ entry (SOCE) mechanisms. To commemorate the 7th decade after being coined, we comprehensively and critically reviewed "old", historical landmarks and well-established concepts, and blended them with recent advances to have a complete, quantitative-focused landscape of the ECC. We discuss the: 1) elucidation of the CRU structures at near-atomic resolution and its implications for functional coupling; 2) reliable quantification of peak sarcoplasmic [Ca2+] using fast, low affinity Ca2+ dyes and the relative contributions of the Ca2+-binding mechanisms to the whole concert of Ca2+ fluxes inside the fibre; 3) articulation of this novel quantitative information with the unveiled structural details of the molecular machinery involved in mitochondrial Ca2+ handing to understand how and how much Ca2+ enters the mitochondria; 4) presence of the SOCE machinery and its different modes of activation, which awaits understanding of its magnitude and relevance in situ; 5) pharmacology of the ECC, and 6) emerging topics such as the use and potential applications of super-resolution and induced pluripotent stem cells (iPSC) in ECC. Blending the old with the new works better!
    Keywords:  Ca2+; Ca2+ channels; excitation-contraction coupling; fluorescence; mitochondria; ryanodine receptor—RYR1; skeletal muscle
    DOI:  https://doi.org/10.3389/fphys.2022.989796
  12. Nutrition. 2022 Aug 12. pii: S0899-9007(22)00227-1. [Epub ahead of print]103-104 111814
    Ketogenic diet attenuates post-cardiac arrest brain injury by upregulation of pentose phosphate pathway-mediated antioxidant defense in a mouse model of cardiac arrest.
    Fei Peng, Yu-Han Zhang, Lu Zhang, Man Yang, Chan Chen, Hai Yu, Tao Li.
       OBJECTIVE: The aim of this study was to investigate the effect of the ketogenic diet (KD) on post-cardiac arrest brain injury in a mouse model of cardiac arrest and cardiopulmonary resuscitation.
    METHODS: Mice were fed a KD for 4 wk and then subjected to cardiac arrest and cardiopulmonary resuscitation. The HT22 cells after β-hydroxybutyrate (β-OHB) treatment were exposed to oxygen-glucose deprivation/reoxygenation. Survival and neurologic function were measured after return of spontaneous circulation. Positron emission tomography/computed tomography scanning, 13C-magnetic resonance spectroscopy analysis, and seahorse assay were performed to explore the mechanism underlying the phenotype.
    RESULTS: Results of this study demonstrated that KD improved neurologic function and reduced apoptotic neurons in cardiac arrest and cardiopulmonary resuscitation mice. With no alteration of glucose uptake, KD suppressed glucose oxidation in mouse brain. Consistently, the glycolytic capacity of the HT22 cells was also downregulated by β-OHB treatment. Moreover, KD increased nicotinamide adenine dinucleotide phosphate/oxidized nicotinamide adenine dinucleotide phosphate and reduced glutathione/oxidized glutathione couples and reduced reactive oxygen species in the brain, probably due to activation of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway. Pharmacologic inhibition of pentose phosphate pathway totally abolished the influence of β-OHB on glycolysis, and post-oxygen-glucose deprivation/reoxygenation cell viability and reactive oxygen species production in HT22 cells.
    CONCLUSION: KD improved survival and attenuated post-cardiac arrest brain injury, which was mediated by upregulation of pentose phosphate pathway and related antioxidant defense system.
    Keywords:  Cardiac arrest; Glucose metabolism; Ketogenic diet; Pentose phosphate pathway; Post-cardiac arrest brain injury
    DOI:  https://doi.org/10.1016/j.nut.2022.111814
  13. Int J Environ Res Public Health. 2022 Sep 14. pii: 11542. [Epub ahead of print]19(18):
    The Effects of Concurrent Training Combined with Low-Carbohydrate High-Fat Ketogenic Diet on Body Composition and Aerobic Performance: A Systematic Review and Meta-Analysis.
    Yubo Wang, Kaixiang Zhou, Vienna Wang, Dapeng Bao, Junhong Zhou.
      (1) Background: Recently, studies have emerged to explore the effects of concurrent training (CT) with a low-carb, high-fat ketogenic diet (LCHF) on body composition and aerobic performance and observed its benefits. However, a large variance in the study design and observations is presented, which needs to be comprehensively assessed. We here thus completed a systematic review and meta-analysis to characterize the effects of the intervention combining CT and LCHF on body composition and aerobic capacity in people with training experience as compared to that combining CT and other dietary strategies. (2) Methods: A search strategy based on the PICOS principle was used to find literature in the databases of PubMed, Web of Science, EBSCO, Sport-discuss, and Medline. The quality and risk of bias in the studies were independently assessed by two researchers. (3) Result: Eight studies consisting of 170 participants were included in this work. The pooled results showed no significant effects of CT with LCHF on lean mass (SMD = -0.08, 95% CI -0.44 to 0.3, p = 0.69), body fat percentage (SMD = -0.29, 95% CI -0.66 to 0.08, p = 0.13), body mass (SMD = -0.21, 95% CI -0.53 to 0.11, p = 0.2), VO2max (SMD = -0.01, 95% CI -0.4 to 0.37, p = 0.95), and time (or distance) to complete the aerobic tests (SMD = -0.02, 95% CI -0.41 to 0.37, p = 0.1). Subgroup analyses also showed that the training background of participants (i.e., recreationally trained participants or professionally trained participants) and intervention duration (e.g., > or ≤six weeks) did not significantly affect the results. (4) Conclusions: This systematic review and meta-analysis provide evidence that compared to other dietary strategies, using LCHF with CT cannot induce greater benefits for lean mass, body fat percentage, body mass, VO2max, and aerobic performance in trained participants.
    Keywords:  aerobic performance; athletes; body composition; concurrent training; high-fat ketogenic diet; low-carb
    DOI:  https://doi.org/10.3390/ijerph191811542
  14. J Gerontol A Biol Sci Med Sci. 2022 Sep 23. pii: glac201. [Epub ahead of print]
    Increased Efficiency of Mitochondrial Coupling with a Reduction in Other Mitochondrial Respiratory Parameters in Peripheral Blood Mononuclear Cells is Observed in Older Adults.
    Sirawit Sriwichaiin, Nattayaporn Apaijai, Arintaya Phrommintikul, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Wasana Pratchayasakul, Nisakron Thongmung, Usanee Mahantassanapong, Prin Vathesatogkit, Chagriya Kitiyakara, Piyamitr Sritara, Nipon Chattipakorn, Siriporn C Chattipakorn.
      Mitochondrial dysfunction is a factor potentially contributing to the aging process. However, evidence surrounding changes in mitochondrial function and aging is still limited, therefore this study aimed to investigate further the association between them. Possible confounding factors were included in the statistical analysis to explore the possibility of any independent associations. One thousand seven hundred and sixty-nine participants (619 middle-aged adults (age<65) and 1,150 older adults (age≥65)) from the Electricity Generating Authority of Thailand were enrolled onto the study. The clinical characteristics and medical history were collected. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and used for analysis of mitochondrial function. Several parameters pertinent to mitochondrial respiration including non-mitochondrial respiration, basal respiration, maximal respiration, proton leak, and spare respiratory capacity were found to be two to three times lower in the mitochondria isolated from the cells of older adults. Interestingly, the mitochondrial ATP production was only slightly reduced, and the percentage of coupling efficiency of PBMC mitochondria was significantly higher in the older adult group. The mitochondrial mass and oxidative stress were significantly reduced in older adult participants, however, the ratio of oxidative stress to mass was significantly increased. The association of these parameters with age were still shown to be the same from the outcome of the multivariate analyses. The mitochondrial functions and mitochondrial mass in PBMCs were shown to decline in association with age. However, the upregulation of mitochondrial oxidative stress production and mitochondrial coupling efficiency might indicate a compensatory response in mitochondria during aging.
    Keywords:  ATP; PBMCs; mitochondria; oxidative stress
    DOI:  https://doi.org/10.1093/gerona/glac201
  15. Diabetes Metab Syndr Obes. 2022 ;15 2813-2826
    Is Intermittent Fasting Better Than Continuous Energy Restriction for Adults with Overweight and Obesity?
    Ya-Fei Ye, Mei-Xian Zhang, Zhi Lin, Leiwen Tang.
      As a popular weight management intervention, intermittent fasting (IF) has been widely applied to the treatment of overweight and obesity in adults. This review describes the different forms and implementation protocols of IF and their effects on body weight, body composition, cardiometabolic risk factors and other diseases. The existing evidence suggests that IF is as effective as continuous energy restriction and may be a feasible and effective approach to weight loss.
    Keywords:  continuous energy restriction; intermittent fasting; obesity; overweight; weight management
    DOI:  https://doi.org/10.2147/DMSO.S376409
  16. Kidney360. 2022 May 26. 3(5): 843-858
    Iron Supplementation Improves Skeletal Muscle Contractile Properties in Mice with CKD.
    Brent A Momb, Edwin Patino, Oleh M Akchurin, Mark S Miller.
       Background: Patients with chronic kidney disease (CKD) frequently have compromised physical performance, which increases their mortality; however, their skeletal muscle dysfunction has not been characterized at the single-fiber and molecular levels. Notably, interventions to mitigate CKD myopathy are scarce.
    Methods: The effect of CKD in the absence and presence of iron supplementation on the contractile function of individual skeletal muscle fibers from the soleus and extensor digitorum longus muscles was evaluated in 16-week-old mice. CKD was induced by the adenine diet, and iron supplementation was by weekly iron dextran injections.
    Results: Maximally activated and fatigued fiber force production was decreased 24%-52% in untreated CKD, independent of size, by reducing strongly bound myosin/actin cross-bridges and/or decreasing myofilament stiffness in myosin heavy chain (MHC) I, IIA, and IIB fibers. Additionally, myosin/actin interactions in untreated CKD were slower for MHC I and IIA fibers and unchanged or faster in MHC IIB fibers. Iron supplementation improved anemia and did not change overall muscle mass in CKD mice. Iron supplementation ameliorated CKD-induced myopathy by increasing strongly bound cross-bridges, leading to improved specific tension, and/or returning the rate of myosin/actin interactions toward or equivalent to control values in MHC IIA and IIB fibers.
    Conclusions: Skeletal muscle force production was significantly reduced in untreated CKD, independent of fiber size, indicating that compromised physical function in patients is not solely due to muscle mass loss. Iron supplementation improved multiple aspects of CKD-induced myopathy, suggesting that timely correction of iron imbalance may aid in ameliorating contractile deficits in CKD patients.
    Keywords:  basic science; chronic kidney disease; frailty; iron; kidney; mice; myosin; physical function
    DOI:  https://doi.org/10.34067/KID.0004412021
  17. Int J Mol Sci. 2022 Sep 13. pii: 10660. [Epub ahead of print]23(18):
    The Effect of Uridine on the State of Skeletal Muscles and the Functioning of Mitochondria in Duchenne Dystrophy.
    Mikhail V Dubinin, Vlada S Starinets, Natalia V Belosludtseva, Irina B Mikheeva, Yuliya A Chelyadnikova, Daria K Penkina, Alexander A Vedernikov, Konstantin N Belosludtsev.
      Duchenne muscular dystrophy is caused by the loss of functional dystrophin that secondarily causes systemic metabolic impairment in skeletal muscles and cardiomyocytes. The nutraceutical approach is considered as a possible complementary therapy for this pathology. In this work, we have studied the effect of pyrimidine nucleoside uridine (30 mg/kg/day for 28 days, i.p.), which plays an important role in cellular metabolism, on the development of DMD in the skeletal muscles of dystrophin deficient mdx mice, as well as its effect on the mitochondrial dysfunction that accompanies this pathology. We found that chronic uridine administration reduced fibrosis in the skeletal muscles of mdx mice, but it had no effect on the intensity of degeneration/regeneration cycles and inflammation, pseudohypetrophy, and muscle strength of the animals. Analysis of TEM micrographs showed that uridine also had no effect on the impaired mitochondrial ultrastructure of mdx mouse skeletal muscle. The administration of uridine was found to lead to an increase in the expression of the Drp1 and Parkin genes, which may indicate an increase in the intensity of organelle fission and the normalization of mitophagy. Uridine had little effect on OXPHOS dysfunction in mdx mouse mitochondria, and moreover, it was suppressed in the mitochondria of wild type animals. At the same time, uridine restored the transport of potassium ions and reduced the production of reactive oxygen species; however, this had no effect on the impaired calcium retention capacity of mdx mouse mitochondria. The obtained results demonstrate that the used dose of uridine only partially prevents mitochondrial dysfunction in skeletal muscles during Duchenne dystrophy, though it mitigates the development of destructive processes in skeletal muscles.
    Keywords:  Duchenne muscular dystrophy; lipid peroxidation; mitochondria; mitochondrial dysfunction; potassium transport; skeletal muscle; uridine
    DOI:  https://doi.org/10.3390/ijms231810660
  18. Transpl Immunol. 2022 Sep 17. pii: S0966-3274(22)00192-7. [Epub ahead of print] 101718
    NLRP3 inflammasome: A potential therapeutic target to minimize renal ischemia/reperfusion injury during transplantation.
    Xiaochen Su, Bin Liu, Shangguo Wang, Yuxiong Wang, Zehua Zhang, Honglan Zhou, Faping Li.
      Renal transplantation is currently the best treatment option for patients with end-stage kidney disease. Ischemia/reperfusion injury (IRI), which is an inevitable event during renal transplantation, has a profound impact on the function of transplanted kidneys. It has been well demonstrated that innate immune system plays an important role in the process of renal IRI. As a critical component of innate immune system, Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has received great attention from scientific community over the past decade. The main function of NLRP3 inflammasome is mediating activation of caspase-1 and maturation of interleukin (IL)-1β and IL-18. In this review, we summarize the associated molecular signaling events about NLRP3 inflammasome in renal IRI, and highlight the possibility of targeting NLRP3 inflammasome to minimize renal IRI during transplantation.
    Keywords:  Caspase-1; Ischemia/reperfusion injury; NLRP3 inflammasome; Renal transplantation
    DOI:  https://doi.org/10.1016/j.trim.2022.101718
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