bims-kimdis 2023-07-09 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023–07–09
28 papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins

Ketogenic Diet in Heart Failure: Fact or Fiction?
Ketogenic diets for obesity-hypoventilation syndrome? Interesting physiology but a long way to go.
Starvation Ketoacidosis in a Young Healthy Female After Prolonged Religious Fasting.
Not all very-low-carbohydrate diets are created equal.
Ketogenic diet inhibits neointimal hyperplasia by suppressing oxidative stress and inflammation.
Ketogenic Diet as a Possible Non-pharmacological Therapy in Main Endocrine Diseases of the Female Reproductive System: A Practical Guide for Nutritionists.
Effect of the ketogenic diet as a treatment for refractory epilepsy in children and adolescents: a systematic review of reviews.
Age and sex dependent effects of metabolic response to muscle contraction.
The role of intermittent fasting and the ketogenic diet in cancer disease: can they replace the Mediterranean diet?
CISD3 is required for Complex I function, mitochondrial integrity, and skeletal muscle maintenance.
Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis.
Fasting No Better Than Calorie Counting for Weight Loss.
Nutritional Strategies for Endurance Cyclists - Periodized Nutrition, Ketogenic Diets, and Other Considerations.
Extracellular messaging elicited by exercise.
Oxygen consumption rate to evaluate mitochondrial dysfunction and toxicity in cardiomyocytes.
Physical performance during energy deficiency in humans: An evolutionary perspective.
Resistance training prescription for muscle strength and hypertrophy in healthy adults: a systematic review and Bayesian network meta-analysis.
To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?
Glucose loading for heart failure protects the myocardium and improves physical function.
Medium chain triglycerides with a C8:C10 ratio of 30:70 enhances cognitive performance and mitigates the cognitive decline associated with prolonged exercise in young and healthy adults.
Blood-based bioenergetics: a liquid biopsy of mitochondrial dysfunction in disease.
Mitochondrial dysfunction in the offspring of obese mothers and it's transmission through damaged oocyte mitochondria: Integration of mechanisms.
An Improved Method to Isolate Mitochondrial Contact Sites.
Role of proprioceptors in chronic musculoskeletal pain.
The role of cannabidiol in aging.
The mitochondrial calcium uniporter transports Ca 2+ via a ligand-relay mechanism.
Quercetin supplementation promotes recovery after exercise-induced muscle damage: a systematic review and meta-analysis of randomized controlled trials.
Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.

JACC Heart Fail. 2023 07;pii: S2213-1779(23)00241-X. [Epub ahead of print]11(7): 838-844

Ketogenic Diet in Heart Failure: Fact or Fiction?

Nandan Kodur, Salva Yurista, Valesha Province, Emma Rueth, Christopher Nguyen, W H Wilson Tang.



Keywords:  heart failure; ketogenic diet; ketone bodies

DOI:  https://doi.org/10.1016/j.jchf.2023.05.009
Respirology. 2023 Jul 02.

Ketogenic diets for obesity-hypoventilation syndrome? Interesting physiology but a long way to go.

Elizabeth Anne Cayanan, Ronald R Grunstein.



Keywords:  ketogenic diet; ketosis; low-carbohydrate diet; obesity hypoventilation syndrome; sleep

DOI:  https://doi.org/10.1111/resp.14540
Cureus. 2023 Jun;15(6): e39962

Starvation Ketoacidosis in a Young Healthy Female After Prolonged Religious Fasting.

Ramanathan Ramesh, Arulmoly Kanagasingam, Sithy Sabrina, Uthayakumar Anushanth.

  Ketone bodies are important energy sources for the body and are produced by the liver when the body is in a deficiency state of glucose, which is used in the peripheral tissues to provide energy. There are several ketone bodies that are produced by the liver, of which two are important: acetoacetate and beta-hydroxybutyrate. Even though ketone bodies are always present in the body, they are minimal when a person is not fasting. Ketone bodies are produced by the oxidation of fatty acids to fulfill the metabolic needs of tissues, especially the brain. The biochemical reactions of forming ketone bodies are triggered by a lack of insulin and an elevated glucagon level in the blood. Both cause unopposed lipolysis and free fatty acid oxidation resulting in the production of ketone bodies and eventually high anion gap metabolic acidosis. We present a case of young healthy female who presented with euglycemic ketoacidosis after involving prolonged fasting for her religious ceremony. She also physically exerted quite more during her fasting. With a detailed history and excluding other possibilities, we made the diagnosis of starvation ketoacidosis. She improved well with the treatment and established her pre-morbid condition in our review.

Keywords:  euglycemia; hypoglycemia; ketoacidosis; metabolic acidosis; starvation

DOI:  https://doi.org/10.7759/cureus.39962
Diabetologia. 2023 Jul 05.

Not all very-low-carbohydrate diets are created equal.

Caterina Conte, Elisabetta Camajani, Alessio Lai, Massimiliano Caprio.



Keywords:  Ketogenic diet; Obesity; Type 2 diabetes; Weight loss

DOI:  https://doi.org/10.1007/s00125-023-05961-0
Clin Exp Hypertens. 2023 Dec 31. 45(1): 2229538

Ketogenic diet inhibits neointimal hyperplasia by suppressing oxidative stress and inflammation.

Xuefei Xu, Limin Xie, Lili Chai, Xiaoming Wang, Jinhu Dong, Jipei Wang, Pengwei Yang.

   OBJECTIVE: Neointimal hyperplasia is the primary mechanism underlying atherosclerosis and restenosis after percutaneous coronary intervention. Ketogenic diet (KD) exerts beneficial effects in various diseases, but whether it could serve as non-drug therapy for neointimal hyperplasia remains unknown. This study aimed to investigate the effect of KD on neointimal hyperplasia and the potential mechanisms.
METHODS AND RESULTS: Carotid artery balloon-injury model was employed in adult Sprague-Dawley rats to induce neointimal hyperplasia. Then, animals were subjected to either standard rodent chow or KD. For in-vitro experiment, impacts of β-hydroxybutyrate (β-HB), the main mediator of KD effects, on platelet-derived growth factor BB (PDGF-BB) induced vascular smooth muscle cell (VSMC) migration and proliferation were determined. Balloon injury induced event intimal hyperplasia and upregulation of protein expression of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA), and these changes were significantly ameliorated by KD. In addition, β-HB could markedly inhibit PDGF-BB induced VMSC migration and proliferation, as well as inhibiting expressions of PCNA and α-SMC. Furthermore, KD inhibited balloon-injury induced oxidative stress in carotid artery, indicated by reduced ROS level, malondialdehyde (MDA) and myeloperoxidase (MPO) activities, and increased superoxide dismutase (SOD) activity. We also found balloon-injury induced inflammation in carotid artery was suppressed by KD, indicated by decreased expressions of proinflammatory cytokines IL-1β and TNF-α, and increased expression of anti-inflammatory cytokine IL-10.
CONCLUSION: KD attenuates neointimal hyperplasia through suppressing oxidative stress and inflammation to inhibit VSMC proliferation and migration. KD may represent a promising non-drug therapy for neointimal hyperplasia associated diseases.

Keywords:  Neointimal hyperplasia; inflammation; ketogenic diet; oxidative stress

DOI:  https://doi.org/10.1080/10641963.2023.2229538
Curr Obes Rep. 2023 Jul 05.

Ketogenic Diet as a Possible Non-pharmacological Therapy in Main Endocrine Diseases of the Female Reproductive System: A Practical Guide for Nutritionists.

Elisabetta Camajani, Alessandra Feraco, Ludovica Verde, Eleonora Moriconi, Marco Marchetti, Annamaria Colao, Massimiliano Caprio, Giovanna Muscogiuri, Luigi Barrea.

   PURPOSEOF REVIEW: This narrative review explored the role of ketogenic diets (KDs) in improving fertility outcomes, low-grade inflammation, body weight, visceral adipose tissue, and its potential use in certain types of cancer, through its favorable actions on mitochondrial function, reactive oxygen species generation, chronic inflammation, and tumor growth inhibition. RECENT FINDINGS : Nutrition is crucial to maintain the female reproductive system's health. Evidence on the association between diet and female reproductive system has greatly expanded over the last decade, leading to the identification of specific diet therapy, particularly KDs. KDs has been proved to be an effective weight-loss tool. To date, KDs is being increasingly used in the treatment of many diseases, such as obesity, type 2 diabetes mellitus. KDs is a dietary intervention capable of ameliorating the inflammatory state and oxidative stress through several mechanisms. Due to the increasing use of KDs beyond obesity, this literature review will provide the latest scientific evidence of its possible use in common disorders of the female endocrine-reproductive tract, and a practical guide to its use in these patients.

Keywords:  Endocrine diseases; Female reproductive; Ketogenic diets; Nutritionists; PCOS; VLCKD

DOI:  https://doi.org/10.1007/s13679-023-00516-1
Nutr Rev. 2023 Jul 03. pii: nuad071. [Epub ahead of print]

Effect of the ketogenic diet as a treatment for refractory epilepsy in children and adolescents: a systematic review of reviews.

Cristina Díez-Arroyo, Mónica García-García, María José Soto-Méndez, Esther Molina-Montes, Mercedes Gil-Campos, Ángel Gil, Miriam Gutiérrez-Jimeno, Ángela Hernández-Ruiz.

   CONTEXT: Epilepsy is one of the most prevalent neurological disorders in childhood. Antiepileptic drugs are the preferred treatment. However, 30% of children continue suffering seizures. A ketogenic diet (KD) is one of the emerging alternative treatments.
OBJECTIVE: This review aims to analyze the current evidence regarding the use of a KD for the treatment of refractory epilepsy (RE) in childhood.
DATA SOURCES: A systematic review of reviews was performed, based on MEDLINE (PubMed) as at January 2021.
DATA EXTRACTION: The data extracted included the first author's last name; the year of publication; the country; the study design; the population; the diagnosis, concept, and description of KD types; and major outcome.
RESULTS: Twenty-one reviews were included, 8 with systematic methodology (2 of them included a meta-analysis) and 13 with unsystematic methodology. The main difference between the 2 types of reviews is the reproducibility of their methodology. Therefore, the results of each type of review were analyzed separately. Each type of review described 4 categories of KD: classic KD, modified Atkins diet (MAD), use of medium-chain triglycerides (MCTs), and low glycemic index treatment (LGIT). In terms of effectiveness, the considered systematic reviews reported reductions in the frequency of seizures greater than 50% in about half of the patients. Reviews without systematic methodology reported that 30%-60% of the children showed a 50% or greater reduction in seizures. The most frequently described adverse effects in the 8 systematic reviews were: vomiting (6/8), constipation (6/8), and diarrhea (6/8); and in the unsystematic reviews: vomiting and nausea (10/13), constipation (10/13), and acidosis (9/13).
CONCLUSION: KD can be an effective treatment for RE, with a more than 50% reduction in the frequency of seizures and cognitive improvement being achieved in half of the pediatric patients. The effectiveness of the various types of KD is comparable, and the KD can be adapted to the needs of the patient.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021244142.

Keywords:  anticonvulsants; diet therapy; ketogenic diet; refractory epilepsy; seizures

DOI:  https://doi.org/10.1093/nutrit/nuad071
bioRxiv. 2023 Jun 01. pii: 2023.05.30.542769. [Epub ahead of print]

Age and sex dependent effects of metabolic response to muscle contraction.

Matthew D Campbell, Danijel Djukovic, Daniel Raftery, David Marcinek.

Sarcopenia, the age-related loss of muscle mass and function, contributes to decreased quality of life in the elderly and increased healthcare costs. Decreased skeletal muscle mass, specific force, increased overall fatty depositions in the skeletal muscle, frailty and depressed energy maintenance are all associated with increased oxidative stress and the decline in mitochondrial function with age. We hypothesized that elevated mitochondrial stress with age alters the capacity of mitochondria to utilize different substrates following muscle contraction. To test this hypothesis, we designed two in vivo muscle-stimulation protocols to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise to characterize the effect of age and sex on mitochondrial substrate utilization in skeletal muscle following muscle contraction. Following HII stimulation, mitochondria from young skeletal muscle increased fatty acid oxidation compared to non-stimulated control muscle; however, mitochondria from aged muscle decreased fatty acid oxidation. In contrast, following LISS, mitochondrial from young skeletal muscle decreased fatty acid oxidation, whereas aged mitochondria increased fatty acid oxidation. We also found that HII can inhibit mitochondrial oxidation of glutamate in both stimulated and non-stimulated aged muscle, suggesting HII initiates circulation of an exerkine capable of altering whole-body metabolism. Analyses of the muscle metabolome indicates that changes in metabolic pathways induced by HII and LISS contractions in young muscle are absent in aged muscle. Treatment with elamipretide, a mitochondrially targeted peptide, restored glutamate oxidation and metabolic pathway changes following HII suggesting rescuing redox status and improving mitochondrial function in aged muscle enhances the metabolic response to muscle contraction.

DOI: https://doi.org/10.1101/2023.05.30.542769
Eur J Cancer Prev. 2023 Jul 03.

The role of intermittent fasting and the ketogenic diet in cancer disease: can they replace the Mediterranean diet?

Aleyna Nur Küçük, Seda Çiftçi.

The prevalence of cancer is rising globally, and it is the second leading cause of death. Nutrition has an important influence on the risk of developing cancer. Moreover, changes in the gut microbiota are connected to the risk of developing cancer and are critical for sustaining immunity. Various studies have shown that intermittent fasting, ketogenic diet, and the Mediterranean diet are effective therapies in changing the intestinal microbiota, the prevention of cancer, and the improvement of tolerance to treatment in cancer patients. Although there is not enough evidence to show that the ketogenic diet is effective in changing the intestinal microbiota in a manner that could prevent cancer, intermittent fasting and the Mediterranean diet could positively affect composition of intestinal microbiota against cancer. In addition, the ketogenic diet, intermittent fasting, and the Mediterranean diet have the potential to stimulate anticarcinogenic pathways, and they might increase cancer patients' quality of life according to scientific evidence. In this review, we represent and argue recent scientific data on relationship between intermittent fasting, the ketogenic diet, and the Mediterranean diet, intestinal microbiota, cancer prevention and cancer treatment.

DOI: https://doi.org/10.1097/CEJ.0000000000000820
bioRxiv. 2023 Jun 04. pii: 2023.06.03.543558. [Epub ahead of print]

CISD3 is required for Complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Henri-Baptiste Marjault, Ola Karmi, Linda Rowland, Thi Thao Nguyen, DeAna Grant, Camila Manrique-Acevedo, Rachel Nechushtai, Ron Mittler.

Mitochondria play a central role in muscle metabolism and function. In skeletal muscles, a unique family of iron-sulfur proteins, termed CISD proteins, support mitochondrial function. The abundance of these proteins declines with aging leading to muscle degeneration. Although the function of the outer mitochondrial proteins CISD1 and CISD2 has been defined, the role of the inner mitochondrial protein CISD3, is currently unknown. Here we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne Muscular Dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscle mitochondria, and that CISD3 interacts with, and donates its clusters to, Complex I respiratory chain subunit NDUFV2. These findings reveal that CISD3 is important for supporting the biogenesis and function of Complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact muscle degeneration syndromes, aging, and related conditions.

DOI: https://doi.org/10.1101/2023.06.03.543558
Front Nutr. 2023 ;10 1126534

Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis.

Angela G Juby, Stephen C Cunnane, Diana R Mager.

  COVID-19 infection causes cognitive changes in the acute phase, but also after apparent recovery. Over fifty post (long)-COVID symptoms are described, including cognitive dysfunction ("brain fog") precluding return to pre-COVID level of function, with rates twice as high in females. Additionally, the predominant demographic affected by these symptoms is younger and still in the workforce. Lack of ability to work, even for six months, has significant socio-economic consequences. This cognitive dysfunction is associated with impaired cerebral glucose metabolism, assessed using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing brain regions that are abnormal compared to age and sex matched controls. In other cognitive conditions such as Alzheimer's disease (AD), typical patterns of cerebral glucose hypometabolism, frontal hypometabolism and cerebellar hypermetabolism are common. Similar FDG-PET changes have also been observed in post-COVID-19, raising the possibility of a similar etiology. Ketone bodies (B-hydroxybutyrate, acetoacetate and acetone) are produced endogenously with very low carbohydrate intake or fasting. They improve brain energy metabolism in the face of cerebral glucose hypometabolism in other conditions [mild cognitive impairment (MCI) and AD]. Long-term low carbohydrate intake or prolonged fasting is not usually feasible. Medium chain triglyceride (MCT) is an exogenous route to nutritional ketosis. Research has supported their efficacy in managing intractable seizures, and cognitive impairment in MCI and AD. We hypothesize that cerebral glucose hypometabolism associated with post COVID-19 infection can be mitigated with MCT supplementation, with the prediction that cognitive function would also improve. Although there is some suggestion that post COVID-19 cognitive symptoms may diminish over time, in many individuals this may take more than six months. If MCT supplementation is able to speed the cognitive recovery, this will impact importantly on quality of life. MCT is readily available and, compared to pharmaceutical interventions, is cost-effective. Research shows general tolerability with dose titration. MCT is a component of enteral and parenteral nutrition supplements, including in pediatrics, so has a long record of safety in vulnerable populations. It is not associated with weight gain or adverse changes in lipid profiles. This hypothesis serves to encourage the development of clinical trials evaluating the impact of MCT supplementation on the duration and severity of post COVID-19 cognitive symptoms.

Keywords:  beta-hydroxybutyrate; brain fog; medium chain triglyceride; post (long) COVID-19; subjective cognitive decline

DOI:  https://doi.org/10.3389/fnut.2023.1126534
JAMA. 2023 Jul 05.

Fasting No Better Than Calorie Counting for Weight Loss.

Emily Harris.

DOI: https://doi.org/10.1001/jama.2023.12054
Curr Sports Med Rep. 2023 Jul 01. 22(7): 248-254

Nutritional Strategies for Endurance Cyclists - Periodized Nutrition, Ketogenic Diets, and Other Considerations.

Ryan J Wei, Lindsay Orbeta, Nicholas S Hatamiya, Cindy J Chang.

ABSTRACT: Cycling is a growing sport worldwide since the COVID-19 pandemic. With the growing availability and interest in long distance events, professional and amateur cyclists are pushing themselves further and harder than ever before. Training and nutrition should be understood by the sports medicine professional in order to guide counseling toward proper fueling to avoid health consequences. This article reviews macronutrients and micronutrients, periodized training and nutrition, and the relevance of the ketogenic diet for endurance cyclists riding greater than 90 min.

DOI: https://doi.org/10.1249/JSR.0000000000001085
Sci Signal. 2023 07 04. 16(792): eadj4169

Extracellular messaging elicited by exercise.

Wei Wong.

The exercise-induced secretomes of multiple cell types in mice are characterized.

DOI: https://doi.org/10.1126/scisignal.adj4169
Toxicol Res. 2023 Jul;39(3): 333-339

Oxygen consumption rate to evaluate mitochondrial dysfunction and toxicity in cardiomyocytes.

Dohee Ahn, Ryeo-Eun Go, Kyung-Chul Choi.

  The increase in the types and complexity of diseases has led to significant advances in diagnostic techniques and the availability of effective therapies. Recent studies have focused on the role of mitochondrial dysfunction in the pathogenesis of cardiovascular diseases (CVDs). Mitochondria are important organelles in cells that generate energy. Besides the production of adenosine triphosphate (ATP), the energy currency of cells, mitochondria are also involved in thermogenesis, control of intracellular calcium ions (Ca2+), apoptosis, regulation of reactive oxygen species (ROS), and inflammation. Mitochondrial dysfunction has been implicated in several diseases including cancer, diabetes, some genetic diseases, and neurogenerative and metabolic diseases. Furthermore, the cardiomyocytes of the heart are rich in mitochondria due to the large energy requirement for optimal cardiac function. One of the main causes of cardiac tissue injuries is believed to be mitochondrial dysfunction, which occurs via complicated pathways which have not yet been completely elucidated. There are various types of mitochondrial dysfunction including mitochondrial morphological change, unbalanced levels of substances to maintain mitochondria, mitochondrial damage by drugs, and mitochondrial deletion and synthesis errors. Most of mitochondrial dysfunctions are linked with symptoms and diseases, thus we focus on parts of mitochondrial dysfunction about fission and fusion in cardiomyocytes, and ways to understand the mechanism of cardiomyocyte damage by detecting oxygen consumption levels in the mitochondria.

Keywords:  Cardiomyocytes; Mitochondrial dysfunction; Mitochondrial fission; Oxygen consumption rate

DOI:  https://doi.org/10.1007/s43188-023-00183-3
Comp Biochem Physiol A Mol Integr Physiol. 2023 Jul 03. pii: S1095-6433(23)00106-X. [Epub ahead of print] 111473

Physical performance during energy deficiency in humans: An evolutionary perspective.

José L Areta.

  Energy deficiency profoundly disrupts normal endocrinology, metabolism, and physiology, resulting in an orchestrated response for energy preservation. As such, despite energy deficit is typically thought as positive for weight-loss and treatment of cardiometabolic diseases during the current obesity pandemic, in the context of contemporary sports and exercise nutrition, chronic energy deficiency is associated to negative health and athletic performance consequences. However, the evidence of energy deficit negatively affecting physical capacity and sports performance is unclear. While severe energy deficiency can negatively affect physical capacity, humans can also improve aerobic fitness and strength while facing significant energy deficit. Many athletes, also, compete at an elite and world-class level despite showing clear signs of energy deficiency. Maintenance of high physical capacity despite the suppression of energetically demanding physiological traits seems paradoxical when an evolutionary viewpoint is not considered. Humans have evolved facing intermittent periods of food scarcity in their natural habitat and are able to thrive in it. In the current perspective it is argued that when facing limited energy availability, maintenance of locomotion and physical capacity are of high priority given that they are essential for food procurement for survival in the habitat where humans evolved. When energetic resources are limited, energy may be allocated to tasks essential for survival (e.g. locomotion) while minimising energy allocation to traits that are not (e.g. growth and reproduction). The current perspective provides a model of energy allocation during energy scarcity supported by observation of physiological and metabolic responses that are congruent with this paradigm.

Keywords:  Energy deficit; Evolution; Human performance; Low energy availability; RED-S; Sports nutrition; Triad

DOI:  https://doi.org/10.1016/j.cbpa.2023.111473
Br J Sports Med. 2023 Jul 06. pii: bjsports-2023-106807. [Epub ahead of print]

Resistance training prescription for muscle strength and hypertrophy in healthy adults: a systematic review and Bayesian network meta-analysis.

Brad S Currier, Jonathan C Mcleod, Laura Banfield, Joseph Beyene, Nicky J Welton, Alysha C D'Souza, Joshua A J Keogh, Lydia Lin, Giulia Coletta, Antony Yang, Lauren Colenso-Semple, Kyle J Lau, Alexandria Verboom, Stuart M Phillips.

   OBJECTIVE: To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy.
DATA SOURCES: MEDLINE, Embase, Emcare, SPORTDiscus, CINAHL, and Web of Science were searched until February 2022.
ELIGIBILITY CRITERIA: Randomised trials that included healthy adults, compared at least 2 predefined conditions (non-exercise control (CTRL) and 12 RTx, differentiated by load, sets and/or weekly frequency), and reported muscle strength and/or hypertrophy were included.
ANALYSES: Systematic review and Bayesian network meta-analysis methodology was used to compare RTxs and CTRL. Surface under the cumulative ranking curve values were used to rank conditions. Confidence was assessed with threshold analysis.
RESULTS: The strength network included 178 studies (n=5097; women=45%). The hypertrophy network included 119 studies (n=3364; women=47%). All RTxs were superior to CTRL for muscle strength and hypertrophy. Higher-load (>80% of single repetition maximum) prescriptions maximised strength gains, and all prescriptions comparably promoted muscle hypertrophy. While the calculated effects of many prescriptions were similar, higher-load, multiset, thrice-weekly training (standardised mean difference (95% credible interval); 1.60 (1.38 to 1.82) vs CTRL) was the highest-ranked RTx for strength, and higher-load, multiset, twice-weekly training (0.66 (0.47 to 0.85) vs CTRL) was the highest-ranked RTx for hypertrophy. Threshold analysis demonstrated these results were extremely robust.
CONCLUSION: All RTx promoted strength and hypertrophy compared with no exercise. The highest-ranked prescriptions for strength involved higher loads, whereas the highest-ranked prescriptions for hypertrophy included multiple sets.
PROSPERO REGISTRATION NUMBER: CRD42021259663 and CRD42021258902.

Keywords:  aging; muscle; muscle, skeletal; weight lifting

DOI:  https://doi.org/10.1136/bjsports-2023-106807
PLoS Pathog. 2023 Jul;19(7): e1011471

To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?

Jérémy Verbeke, Xavier De Bolle, Thierry Arnould.

Mitochondria fulfil a plethora of cellular functions ranging from energy production to regulation of inflammation and cell death control. The fundamental role of mitochondria makes them a target of choice for invading pathogens, with either an intracellular or extracellular lifestyle. Indeed, the modulation of mitochondrial functions by several bacterial pathogens has been shown to be beneficial for bacterial survival inside their host. However, so far, relatively little is known about the importance of mitochondrial recycling and degradation pathways through mitophagy in the outcome (success or failure) of bacterial infection. On the one hand, mitophagy could be considered as a defensive response triggered by the host upon infection to maintain mitochondrial homeostasis. However, on the other hand, the pathogen itself may initiate the host mitophagy to escape from mitochondrial-mediated inflammation or antibacterial oxidative stress. In this review, we will discuss the diversity of various mechanisms of mitophagy in a general context, as well as what is currently known about the different bacterial pathogens that have developed strategies to manipulate the host mitophagy.

DOI: https://doi.org/10.1371/journal.ppat.1011471
J Phys Ther Sci. 2023 Jul;35(7): 542-546

Glucose loading for heart failure protects the myocardium and improves physical function.

Ryoichi Nishida, Jun Goto, Noboru Kamajiri, Shogo Terayama, Mimo Shirahase, Hidetaka Imagita.

  [Purpose] The purpose of this study was to investigate the effects of glucose intake on physical function in a heart failure rat model. [Materials and Methods] Five-week-old male Wistar rats were used for this study. Monocrotalin (40 mg/kg) was administered intraperitoneally to rats to induce heart failure. The rats were divided into two groups, control and MCT; the MCT group was further classified according to glucose concentration (0%, 10%, and 50%). [Results] Glucose intake during heart failure prevented the loss of body weight, skeletal muscle, and fat mass. Myocardial metabolism in heart failure was enhanced by hypoxia, which in turn, enhanced the glycolytic system. [Conclusion] Glucose loading suppressed cardiac hypertrophy and improved physical function in the heart failure rat model.

Keywords:  Cardiac cachexia; Heart failure; Myocardium metabolism

DOI:  https://doi.org/10.1589/jpts.35.542
Physiol Behav. 2023 Jun 30. pii: S0031-9384(23)00209-3. [Epub ahead of print]269 114284

Medium chain triglycerides with a C8:C10 ratio of 30:70 enhances cognitive performance and mitigates the cognitive decline associated with prolonged exercise in young and healthy adults.

Jake S Ashton, James W Roberts, Caroline J Wakefield, Don P M MacLaren, Simon Marwood, James J Malone.

   INTRODUCTION: Prolonged exercise has been linked to a decline in cognitive function due to a variety of factors, such as a drop in oxygen in the prefrontal cortex and an increase in stress hormones and neurotransmitters. Medium chain triglycerides (MCTs) may possibly offset this decline as they provide energy for the brain via both direct and indirect pathways, alongside promoting chronic physiological adaptations within the brain.
METHODS: Participants were divided into two groups; MCT (n = 9) and Placebo (n = 10). The MCT gels contained 6 g of MCT with a C8:C10 ratio of 30:70, whereas the placebo gels contained carbohydrates of similar calorific value to the MCT gels. Participants visited the laboratory on three occasions (familiarisation/fitness test, pre-supplementation, post-supplementation), during which they performed a battery of cognitive tasks assessing domains such as processing speed, working memory, selective attention, decision making and coordination, before and after a prolonged bout of exercise (60 mins at 90% gas exchange threshold (GET). A 2-week supplementation period between visits 2 and 3 involved the ingestion of 2 gels per day.
RESULTS: Exercise resulted in detriments in most cognitive tasks pre-supplementation for both groups, and post-supplementation for the Placebo group (main effect ps< 0.05). Post-supplementation, the effect of exercise was mediated in the MCT group for all cognitive tasks (main effect ps< 0.05), except for the Digit and Spatial Span Backwards test phases (main effect ps> 0.05). Furthermore, MCT supplementation enhanced before-exercise cognitive performance and in some measures, such as working memory, this was maintained after-exercise (interaction effect ps> 0.05).
CONCLUSIONS: Chronic MCT supplementation enhanced before-exercise cognitive performance and offset the cognitive decline caused by a prolonged bout of exercise. In some cases, improvements in before-exercise cognitive performance were maintained after-exercise.

Keywords:  Brain; Cognition; Gas exchange threshold; MCTs; Prolonged exercise

DOI:  https://doi.org/10.1016/j.physbeh.2023.114284
Trends Endocrinol Metab. 2023 Jul 04. pii: S1043-2760(23)00115-7. [Epub ahead of print]

Blood-based bioenergetics: a liquid biopsy of mitochondrial dysfunction in disease.

Mia S Wilkinson, Kimberly J Dunham-Snary.

  Mitochondria operate as hubs of cellular metabolism that execute important regulatory functions. Damaged/dysfunctional mitochondria are recognized as major pathogenic contributors to many common human diseases. Assessment of mitochondrial function relies upon invasive tissue biopsies; peripheral blood cells, specifically platelets, have emerged as an ideal candidate for mitochondrial function assessment. Accessibility and documented pathology-related dysfunction have prompted investigation into the role of platelets in disease, the contribution of platelet mitochondria to pathophysiology, and the capacity of platelets to reflect systemic mitochondrial health. Platelet mitochondrial bioenergetics are being investigated in neurodegenerative and cardiopulmonary diseases, infection, diabetes, and other (patho)physiological states such as aging and pregnancy. Early findings support the use of platelets as a biomarker for mitochondrial functional health.

Keywords:  bioenergetics; biomarker; metabolism; mitochondria; platelet

DOI:  https://doi.org/10.1016/j.tem.2023.06.004
Biochim Biophys Acta Mol Basis Dis. 2023 Jul 04. pii: S0925-4439(23)00168-0. [Epub ahead of print] 166802

Mitochondrial dysfunction in the offspring of obese mothers and it's transmission through damaged oocyte mitochondria: Integration of mechanisms.

A L Elías-López, O Vázquez-Mena, A N Sferruzzi-Perri.

  In vivo and in vitro studies demonstrate that mitochondria in the oocyte, are susceptible to damage by suboptimal pre/pregnancy conditions, such as obesity. These suboptimal conditions have been shown to induce mitochondrial dysfunction (MD) in multiple tissues of the offspring, suggesting that mitochondria of oocytes that pass from mother to offspring, can carry information that can programme mitochondrial and metabolic dysfunction of the next generation. They also suggest that transmission of MD could increase the risk of obesity and other metabolic diseases in the population inter- and trans-generationally. In this review, we examined whether MD observed in offspring tissues of high energetic demand, is the result of the transmission of damaged mitochondria from obese mothers' oocytes to the offspring. The contribution of genome-independent mechanisms (namely mitophagy) in this transmission were also explored. Finally, potential interventions aimed at improving oocyte/embryo health were investigated, to see if they may provide an opportunity to halter the generational effects of MD.

Keywords:  Downregulated mitophagy; Maternal obesity; Metabolic dysfunction; Milpa diet; Mitochondrial metabolic dysfunction; Mitophagy; Offspring mitochondrial dysfunction; Oocyte mitochondria; Preconceptional interventions; Traditional diet

DOI:  https://doi.org/10.1016/j.bbadis.2023.166802
J Vis Exp. 2023 06 16.

An Improved Method to Isolate Mitochondrial Contact Sites.

Siavash Khosravi, Johanna Frickel, Max E Harner.

Mitochondria are present in virtually all eukaryotic cells and perform essential functions that go far beyond energy production, for instance, the synthesis of iron-sulfur clusters, lipids, or proteins, Ca2+ buffering, and the induction of apoptosis. Likewise, mitochondrial dysfunction results in severe human diseases such as cancer, diabetes, and neurodegeneration. In order to perform these functions, mitochondria have to communicate with the rest of the cell across their envelope, which consists of two membranes. Therefore, these two membranes have to interact constantly. Proteinaceous contact sites between the mitochondrial inner and outer membranes are essential in this respect. So far, several contact sites have been identified. In the method described here, Saccharomyces cerevisiae mitochondria are used to isolate contact sites and, thus, identify candidates that qualify for contact site proteins. We used this method to identify the mitochondrial contact site and cristae organizing system (MICOS) complex, one of the major contact site-forming complexes in the mitochondrial inner membrane, which is conserved from yeast to humans. Recently, we further improved this method to identify a novel contact site consisting of Cqd1 and the Por1-Om14 complex.

DOI: https://doi.org/10.3791/65444
Exp Physiol. 2023 Jul 07.

Role of proprioceptors in chronic musculoskeletal pain.

Cheng-Han Lee, Chih-Cheng Chen.

   NEW FINDINGS: What is the topic of this review? Why proprioceptors, which are non-nociceptive, low-threshold mechanosensory neurons that monitor muscle contraction and body position, express several proton-sensing ion channels and receptors. What advances does it highlight? ASIC3 is a dual function protein for proton-sensing and mechano-sensing in proprioceptors that can be activated by eccentric muscle contraction or lactic acidosis. A role is proposed for proprioceptors in non-nociceptive unpleasantness (or sng), which is associated with their acid-sensing properties, in chronic musculoskeletal pain.
ABSTRACT: Proprioceptors are non-nociceptive low-threshold mechanoreceptors. However, recent studies have shown that proprioceptors are acid-sensitive and express a variety of proton-sensing ion channels and receptors. Accordingly, although proprioceptors are commonly known as mechanosensing neurons that monitor muscle contraction status and body position, they may have a role in the development of pain associated with tissue acidosis. In clinical practice, proprioception training is beneficial for pain relief. Here we summarize the current evidence to sketch a different role of proprioceptors in 'non-nociceptive pain' with a focus on their acid-sensing properties.

Keywords:  chronic musculoskeletal pain; glutamate; lactate; muscle spindle; proprioceptors; substance P; tissue acidosis

DOI:  https://doi.org/10.1113/EP090989
Biomed Pharmacother. 2023 Jul 05. pii: S0753-3322(23)00865-X. [Epub ahead of print]165 115074

The role of cannabidiol in aging.

Beibei Ni, Yanying Liu, Meng Dai, Jun Zhao, Yu Liang, Xue Yang, Bing Han, Man Jiang.

  Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.

Keywords:  Age-related diseases; Aging; Cannabidiol; Lifespan; Strategies

DOI:  https://doi.org/10.1016/j.biopha.2023.115074
bioRxiv. 2023 Jun 17. pii: 2023.06.17.545435. [Epub ahead of print]

The mitochondrial calcium uniporter transports Ca 2+ via a ligand-relay mechanism.

Connie Chan, Chen-Ching Yuan, Jason G McCoy, Patrick S Ward, Zenon Grabarek.

The mitochondrial calcium uniporter (mtCU) is a multicomponent Ca 2+ -specific channel that imparts mitochondria with the capacity to sense the cytosolic calcium signals. The metazoan mtCU comprises the pore-forming subunit MCU and the essential regulator EMRE, arranged in a tetrameric channel complex, and the Ca 2+ sensing peripheral proteins MICU1-3. The mechanism of mitochondrial Ca 2+ uptake by mtCU and its regulation is poorly understood. Our analysis of MCU structure and sequence conservation, combined with molecular dynamics simulations, mutagenesis, and functional studies, led us to conclude that the Ca 2+ conductance of MCU is driven by a ligand-relay mechanism, which depends on stochastic structural fluctuations in the conserved DxxE sequence. In the tetrameric structure of MCU, the four glutamate side chains of DxxE (the E-ring) chelate Ca 2+ directly in a high-affinity complex (site 1), which blocks the channel. The four glutamates can also switch to a hydrogen bond-mediated interaction with an incoming hydrated Ca 2+ transiently sequestered within the D-ring of DxxE (site 2), thus releasing the Ca 2+ bound at site 1. This process depends critically on the structural flexibility of DxxE imparted by the adjacent invariant Pro residue. Our results suggest that the activity of the uniporter can be regulated through the modulation of local structural dynamics. A preliminary account of this work was presented at the 67 th Annual Meeting of the Biophysical Society in San Diego, CA, February 18-22, 2023.

DOI: https://doi.org/10.1101/2023.06.17.545435
Biol Sport. 2023 Jul;40(3): 813-825

Quercetin supplementation promotes recovery after exercise-induced muscle damage: a systematic review and meta-analysis of randomized controlled trials.

Daniel Rojano-Ortega, José Peña-Amaro, Antonio J Berral-Aguilar, Francisco J Berral-de la Rosa.

  Quercetin (Q) is one of the most frequently consumed flavonoids in the human diet. The purpose of this systematic review and meta-analysis was to determine the effects of Q supplementation on muscle damage, muscle soreness and biochemical markers of inflammation, antioxidant capacity and oxidative stress after intense exercise. A literature search of SPORTDiscus, PubMed, Web of Science and Scopus was performed from inception to May 31, 2022. Forest plots were generated with fixed or random-effect models and standardized mean differences (SMD). Data extraction and quality assessment were performed independently by two authors. After application of the inclusion and exclusion criteria, 13 studies with a total of 249 sedentary to well-trained participants were included. For all studies there were some concerns about the risk of bias. All but one study used a supplementation dosage of 1000 mg/day. Q supplementation accelerated recovery of muscle function and significantly decreased muscle soreness 0/24 h after exercise (SMD: -1.33; p = 0.03), creatine kinase levels 24/48 h after exercise (SMD: -1.15; p = 0.02), and post-exercise oxidative stress (SMD: -0.92; p = 0.03). However, Q supplementation had no effect on IL-6 concentration. Q supplementation with a dose of 1000 mg/day for periods of more than seven days and a maximum of 12 weeks appears to be a safe and efficacious strategy to reduce muscle damage and muscle soreness, as well as to enhance recovery after intense exercise in sedentary to well-trained young men. Systematic review registration: PROSPERO CRD42021266801.

Keywords:  Dietary supplements; Inflammation; Muscle damage; Muscle soreness; Oxidative stress

DOI:  https://doi.org/10.5114/biolsport.2023.121320
J Transl Med. 2023 Jul 05. 21(1): 441

Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.

Zhen Luo, Jianbo Yao, Zhe Wang, Jianxiong Xu.

  Endothelial cells (ECs) angiogenesis is the process of sprouting new vessels from the existing ones, playing critical roles in physiological and pathological processes such as wound healing, placentation, ischemia/reperfusion, cardiovascular diseases and cancer metastasis. Although mitochondria are not the major sites of energy source in ECs, they function as important biosynthetic and signaling hubs to regulate ECs metabolism and adaptations to local environment, thus affecting ECs migration, proliferation and angiogenic process. The understanding of the importance and potential mechanisms of mitochondria in regulating ECs metabolism, function and the process of angiogenesis has developed in the past decades. Thus, in this review, we discuss the current understanding of mitochondrial proteins and signaling molecules in ECs metabolism, function and angiogeneic signaling, to provide new and therapeutic targets for treatment of diverse cardiovascular and angiogenesis-dependent diseases.

Keywords:  Angiogenesis; Cardiovascular diseases; Endothelial cells; Mitochondrial protein; Signaling pathways

DOI:  https://doi.org/10.1186/s12967-023-04286-1