bims-mifefi 2024-03-31 papers

bims-mifefi

Biomed News

on Mitochondria and female physiology

Issue of 2024–03–31
twenty-two papers selected by
Kayla Vandiver, East Carolina University

Exercise-Regulated Mitochondrial and Nuclear Signalling Networks in Skeletal Muscle.
Creatine and low-dose lithium supplementation separately alter energy expenditure, body mass, and adipose metabolism for the promotion of thermogenesis.
Effects of Follicle Stimulating Hormone on Energy Balance and Tissue Metabolic Health After Loss of Ovarian Function.
Cardiac Mitochondrial Metabolism During Pregnancy and the Postpartum Period.
Mitochondrial Dysfunction as a Factor of Energy Metabolism Disorders in Type 2 Diabetes Mellitus.
High-intensity interval training improves respiratory and cardiovascular adjustments before and after initiation of exercise.
Effect of a 12-Week Multi-Exercise Community Program on Muscle Strength and Lipid Profile in Elderly Women.
The Brain Metabolome Is Modified by Obesity in a Sex-Dependent Manner.
The Correlation between Sex Hormone-Binding Globulin and Clinical Characteristics According to Anti-Müllerian Hormone in Women with Regular Menstrual Cycles: A Prospective Study.
Five Weeks of Sprint Interval Training Improve Muscle Glycolytic Content and Activity But Not Time to Task Failure in Severe Intensity Exercise.
Acute physiological responses and muscle recovery in females: a randomised controlled trial of muscle damaging exercise in hypoxia.
The effect of nutrition education sessions on energy availability, body composition, eating attitude and sports nutrition knowledge in young female endurance athletes.
The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.
Tricarboxylic Acid Cycle Intermediates and Individual Ageing.
Cannabidiol Disrupts Mitochondrial Respiration and Metabolism and Dysregulates Trophoblast Cell Differentiation.
Resting Metabolic Rate and Substrate Utilization during Energy and Protein Availability in Male and Female Athletes.
Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?
Maternal Ezh1/2 deficiency impairs the function of mitochondria in mouse oocytes and early embryos.
The Effect of Oral Adenosine Triphosphate (ATP) Supplementation on Anaerobic Exercise in Healthy Resistance-Trained Individuals: A Systematic Review and Meta-Analysis.
The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium.
Role of polyphenols in remodeling the host gut microbiota in polycystic ovary syndrome.
Insulin signaling and mitochondrial phenotype of skeletal muscle are programmed in utero by maternal diabetes.

Sports Med. 2024 Mar 25.

Exercise-Regulated Mitochondrial and Nuclear Signalling Networks in Skeletal Muscle.

Elizabeth G Reisman, John A Hawley, Nolan J Hoffman.

Exercise perturbs energy homeostasis in skeletal muscle and engages integrated cellular signalling networks to help meet the contraction-induced increases in skeletal muscle energy and oxygen demand. Investigating exercise-associated perturbations in skeletal muscle signalling networks has uncovered novel mechanisms by which exercise stimulates skeletal muscle mitochondrial biogenesis and promotes whole-body health and fitness. While acute exercise regulates a complex network of protein post-translational modifications (e.g. phosphorylation) in skeletal muscle, previous investigations of exercise signalling in human and rodent skeletal muscle have primarily focused on a select group of exercise-regulated protein kinases [i.e. 5' adenosine monophosphate-activated protein kinase (AMPK), protein kinase A (PKA), Ca2+/calmodulin-dependent protein kinase (CaMK) and mitogen-activated protein kinase (MAPK)] and only a small subset of their respective protein substrates. Recently, global mass spectrometry-based phosphoproteomic approaches have helped unravel the extensive complexity and interconnection of exercise signalling pathways and kinases beyond this select group and phosphorylation and/or translocation of exercise-regulated mitochondrial and nuclear protein substrates. This review provides an overview of recent advances in our understanding of the molecular events associated with acute endurance exercise-regulated signalling pathways and kinases in skeletal muscle with a focus on phosphorylation. We critically appraise recent evidence highlighting the involvement of mitochondrial and nuclear protein phosphorylation and/or translocation in skeletal muscle adaptive responses to an acute bout of endurance exercise that ultimately stimulate mitochondrial biogenesis and contribute to exercise's wider health and fitness benefits.

DOI: https://doi.org/10.1007/s40279-024-02007-2
iScience. 2024 Apr 19. 27(4): 109468

Creatine and low-dose lithium supplementation separately alter energy expenditure, body mass, and adipose metabolism for the promotion of thermogenesis.

M S Finch, G L Gardner, J L Braun, M S Geromella, J Murphy, K Colonna, R Dhaliwal, A Retta, A Mohammad, J A Stuart, P J LeBlanc, V A Fajardo, B D Roy, R E K MacPherson.

  Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis. We show that both supplements increase daily energy expenditure (EE) and reduce body mass in male Sprague-Dawley rats. Lithium increased brown adipose tissue (BAT) mitochondrial and lipolytic proteins that are associated with thermogenesis, while creatine increased BAT UCP1 and mitochondrial respiration. The BAT thermogenic findings were not observed in females. White adipose tissue and skeletal muscle markers of thermogenesis were unaltered with the supplements. Together, the data show that low-dose lithium and creatine have diverging effects on markers of BAT thermogenesis and that each increase daily EE and lower body mass in a sex-dependent manner.

Keywords:  Cell biology; Obesity medicine; Physiology

DOI:  https://doi.org/10.1016/j.isci.2024.109468
Am J Physiol Endocrinol Metab. 2024 Mar 27.

Effects of Follicle Stimulating Hormone on Energy Balance and Tissue Metabolic Health After Loss of Ovarian Function.

Andrew E Libby, Claudia Solt, Matthew Jackman, Vanessa Sherk, Rebecca M Foright, Ginger C Johnson, Thi-Tina Nguyen, Matthew Breit, Nicholas Hulett, Michael Rudolph, Paul A Roberson, Elizabeth Wellberg, Purevsuren Jambal, Rebecca L Scalzo, Janine Higgins, T Rajendra Kumar, Margaret E Wierman, Zhaoxing Pan, Kartik Shankar, Dwight J Klemm, Kerrie L Moreau, Wendy M Kohrt, Paul S MacLean.

  Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy. We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the GnRH antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 weeks. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. Additionally, rats administered FSH had reduced liver triglyceride concentration (p<0.001), which correlated with FSH-induced changes at the transcriptomic level. While not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.

Keywords:  Adipose Tissue; Energy Balance; Follicle-Stimulating Hormone; Lipids; Liver

DOI:  https://doi.org/10.1152/ajpendo.00400.2023
Am J Physiol Heart Circ Physiol. 2024 Mar 29.

Cardiac Mitochondrial Metabolism During Pregnancy and the Postpartum Period.

Emily B Schulman-Geltzer, Kyle L Fulghum, Richa A Singhal, Bradford G Hill, Helen E Collins.

  The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-week-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: non-pregnant (NP), mid-pregnancy (MP), late-pregnancy (LP), and 1-week post-birth (PB). Similar to our previous studies, we observed increased heart size during all stages of pregnancy (e.g., MP and LP) and post-birth (e.g., PB) compared with NP mice. Differential cardiac gene and protein expression analyses revealed changes in several mitochondrial transcripts at LP and PB, including several mitochondrial complex subunits and members of the Slc family, important for mitochondrial substrate transport. Respirometry revealed that pyruvate- and glutamate-supported state 3 respiration was significantly higher in PB versus LP mitochondria, with respiratory control ratio (RCR) values higher in PB mitochondria. In addition, we found that PB mitochondria respired more avidly when given 3-hydroxybutyrate (3-OHB) than mitochondria from NP, MP, and LP hearts, with no differences in RCR. These increases in respiration in PB hearts occurred independent of changes in mitochondrial yield, but were associated with higher abundance of 3-hydroxybutyrate dehydrogenase 1. Collectively, these findings suggest that, after birth, maternal cardiac mitochondria have an increased capacity to use 3-OHB, pyruvate, and glutamate as energy sources; however, increases in mitochondrial efficiency in the postpartum heart appear limited to carbohydrate and amino acid metabolism.

Keywords:  3-hydroxybutyrate; female cardiac biology; mitochondrial subunit complexes; physiological hypertrophy; solute transporters

DOI:  https://doi.org/10.1152/ajpheart.00127.2024
Front Biosci (Schol Ed). 2024 Mar 08. 16(1): 5

Mitochondrial Dysfunction as a Factor of Energy Metabolism Disorders in Type 2 Diabetes Mellitus.

Alexander Blagov, Ludmila Nedosugova, Tatiana Kirichenko, Vasily Sukhorukov, Alexandra Melnichenko, Alexander Orekhov.

  The pathogenesis of type 2 diabetes mellitus (T2DM) is based on the development of insulin resistance, which is a disruption to the ability of the tissues to bind to insulin, leading to a general metabolic disorder. Mitochondria are the main participants in cellular energy metabolism, meaning their dysfunction is associated with the development of insulin resistance in T2DM. Mitochondrial function is affected by insulin resistance in various tissues, including skeletal muscle and the liver, which greatly influence glucose homeostasis throughout the body. This review studies mitochondrial dysfunction in T2DM and its impact on disease progression. In addition, it considers the causes underlying the development of mitochondrial dysfunction in T2DM, including mutations in the mitochondrial genome, mitochondrial DNA methylation, and other epigenetic influences, as well as the impact of impaired mitochondrial membrane potential. New therapeutic strategies for diabetes that have been developed to target the mitochondria will also be presented.

Keywords:  glucose; insulin resistance; mitochondrial dysfunction; type 2 diabetes

DOI:  https://doi.org/10.31083/j.fbs1601005
Front Physiol. 2024 ;15 1227316

High-intensity interval training improves respiratory and cardiovascular adjustments before and after initiation of exercise.

Go Ito, Marina Feeley, Toru Sawai, Hideomi Nakata, Shingo Otsuki, Hidehiro Nakahara, Tadayoshi Miyamoto.

  Purpose: High-intensity interval training (HIIT) may induce training-specific physiological adaptations such as improved respiratory and cardiovascular adjustments before and after the onset of high-intensity exercise, leading to improved exercise performance during high-intensity exercise. The present study investigated the effects of HIIT on time-dependent cardiorespiratory adjustment during maximal exercise and before and after initiation of high-intensity exercise, as well as on maximal exercise performance. Methods: 21 healthy male college students were randomly assigned to HIIT group (n = 11) or control group (n = 10). HIIT group performed training on a cycle ergometer once a week for 8 weeks. The training consisted of three bouts of exercise at 95% maximal work rate (WRmax) until exhaustion. Before and after the HIIT program, dynamic cardiorespiratory function was investigated by ramp and step exercise tests, and HIIT-induced cardiac morphological changes were assessed using echocardiography. Results: HIIT significantly improved not only maximal oxygen uptake and minute ventilation, but also maximal heart rate (HR), systolic blood pressure (SBP), and time to exhaustion in both exercise tests (p < 0.05). Time-dependent increases in minute ventilation (VE) and HR before and at the start of exercise were significantly enhanced after HIIT. During high-intensity exercise, there was a strong correlation between percent change (from before to after HIIT program) in time to exhaustion and percent change in HRmax (r = 0.932, p < 0.001). Furthermore, HIIT-induced cardiac morphological changes such as ventricular wall hypertrophy was observed (p < 0.001). Conclusion: We have demonstrated that HIIT at 95% WRmax induces training-specific adaptations such as improved cardiorespiratory adjustments, not only during maximal exercise but also before and after the onset of high-intensity exercise, improvement of exercise performance mainly associated with circulatory systems.

Keywords:  blood pressure; constant-load exercise; heart rate; maximal exercise performance; maximal oxygen uptake; ramp-load exercise

DOI:  https://doi.org/10.3389/fphys.2024.1227316
Nutrients. 2024 Mar 13. pii: 813. [Epub ahead of print]16(6):

Effect of a 12-Week Multi-Exercise Community Program on Muscle Strength and Lipid Profile in Elderly Women.

Hee-Sook Lim, Tae-Hee Kim, Hyun-Joo Kang, Hae-Hyeog Lee.

  This study targeted elderly women over 60 years old (109 persons), divided them into an exercise group and a control group, and implemented a 12-week physical activity program for the exercise group. Body composition, muscle, blood tests, depression, quality of life (QoL), nutritional status, and physical strength were compared and analyzed. The physical activity program was organized through a consultative body of experts, was performed for about 60 min each time in the type and order of exercise appropriate for elderly women, and consisted of a combination of exercise using a band, gymnastics, and stretching. Changes in the muscle index and muscle mass before and after the program were selected as the primary efficacy evaluations. In the exercise group, waist circumference significantly decreased, and the muscle index significantly increased compared to the control group. The number of subjects who showed sarcopenia with a muscle index of 5.4 or less in the exercise group significantly decreased from 22 (38.6%) before program implementation to 13 (22.8%). According to the results of secondary effectiveness evaluation, high-density lipoprotein cholesterol and apolipoprotein (Apo) A were significantly increased in the exercise group compared to the control group, and Apo B, triglyceride, and c-reactive protein showed a significant decrease. Regular physical activity is very important for improving the health and QoL of elderly women, and as a result of applying a customized program, effects such as increased muscle index, improvement of sarcopenia, and improvement of blood lipid status were confirmed. Therefore, it is believed that the physical activity program developed through this study can be applied as a community program for elderly women.

Keywords:  aged; exercise; muscle strength; physical functional performance; sarcopenia; women

DOI:  https://doi.org/10.3390/nu16060813
Int J Mol Sci. 2024 Mar 20. pii: 3475. [Epub ahead of print]25(6):

The Brain Metabolome Is Modified by Obesity in a Sex-Dependent Manner.

Jennifer E Norman, Dragan Milenkovic, Saivageethi Nuthikattu, Amparo C Villablanca.

  Obesity is linked to cognitive decline and metabolic dysregulation in the brain, yet the role of sex is relatively unexplored. We sought to explore the effects of obesity and sex on the brain metabolome. In male and female ob/ob and wild-type mice, we assessed whole brain untargeted metabolomics by liquid chromatography-mass spectrometry, behavior by open field test, and cognitive function by Y-maze and Morris water maze. The metabolic profiles of ob/ob and wild-type mice differed in both sexes. There were more obesity-altered brain metabolites in males than females. Thirty-nine metabolites were unique to males, 15 were unique to females, and five were common to both sexes. Two of the common metabolites were involved in nicotinamide adenine dinucleotide homeostasis. A key feature of the metabolites identified in males was an increase in free fatty acids. In females, a unique feature was the presence of the neuro-modulatory metabolites 2-linoleoyl glycerol and taurine. The behavioral effects of obesity were only seen in females. These results demonstrate that most impacts of obesity on the brain metabolomic profile are sex-specific. Our work has implications for understanding the role of obesity in brain metabolism and the differential contribution of obesity to cognitive decline in males and females.

Keywords:  brain; cognitive function; metabolomics; obesity; sex differences

DOI:  https://doi.org/10.3390/ijms25063475
J Pers Med. 2024 Feb 29. pii: 274. [Epub ahead of print]14(3):

The Correlation between Sex Hormone-Binding Globulin and Clinical Characteristics According to Anti-Müllerian Hormone in Women with Regular Menstrual Cycles: A Prospective Study.

Jihyun Keum, Yong Jin Kim, Sae Kyung Choi, Won Moo Lee, Jaeman Bae.

   BACKGROUND: Polycystic ovarian syndrome (PCOS) can be diagnosed when the anti-Müllerian hormone (AMH) levels are high, but in clinic, women who do not meet the diagnosis of PCOS but have elevated AMH levels are often seen. This study aimed to compare the differences in menstrual cycle patterns and hormone levels in women with regular menstrual cycles, but not PCOS, by dividing them into high and low AMH groups.
MATERIAL AND METHODS: This multicenter prospective study included 68 healthy women. Participants with regular menstrual cycles were divided into two groups according to their AMH levels. The main outcome measures were menstrual cycle pattern, body mass index, and hormone levels (thyroid stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, and free androgen index), which were compared between the groups according to AMH levels. The ovulation was assessed by performing pelvic ultrasound, and by assessing the hormone levels of the luteinizing hormone and progesterone.
RESULTS: The criteria for determining normal and high AMH levels were based on previous literatures. The participants were divided into normal (39 people) and high (29 people) AMH group. No differences were found in age or BMI between the two groups, and no other differences were observed in TSH, prolactin, testosterone, or free androgen index. However, the high AMH group had significantly higher SHBG levels than the normal group (normal group: 65.46 ± 25.78 nmol/L; high group: 87.08 ± 45.05 nmol/L) (p = 0.025).
CONCLUSIONS: This study is the first to analyze the association between SHBG and AMH levels in women with regular menstrual cycles. Elevated AMH levels are associated with increased levels of SHBG levels.

Keywords:  anti-Müllerian hormone; sex hormone-binding globulin; women with regular menstrual cycles

DOI:  https://doi.org/10.3390/jpm14030274
Med Sci Sports Exerc. 2024 Mar 25.

Five Weeks of Sprint Interval Training Improve Muscle Glycolytic Content and Activity But Not Time to Task Failure in Severe Intensity Exercise.

Rodrigo de Araujo Bonetti de Poli, Juan Manuel Murias, Barbara Moura Antunes, Gabriele Marinari, Yago Medeiros Dutra, Fabio Milioni, Alessandro Moura Zagatto.

PURPOSE: This study examined the impact of a 5 weeks sprint interval training (SIT) intervention on time to task failure (TTF) during severe intensity constant work rate (CWR) exercise, as well as in glycolytic enzymatic content and activity, and glycogen content.
METHODS: Fourteen active males were randomized into either a SIT group (n = 8) composed of 15 SIT-sessions over 5 weeks, or a control group (n = 6). At pre-training period, participants performed: i) ramp incremental test to measure the cardiorespiratory function; ii) CWR cycling TTF at 150% of the power output (PO) at the respiratory compensation point (RCP-PO) with muscle biopsies at rest and immediately following task failure. After 5 weeks, the same evaluations were repeated (i.e., exercise intensities matched to current training status), and an additional cycling CWR matched to pre-training 150% RCP-PO was performed only for TTF evaluation. The content and enzymatic activity of glycogen phosphorylase (GPhos), hexokinase (HK), phosphofructokinase (PFK), and lactate dehydrogenase (LDH), as well as the glycogen content, were analyzed. Content of monocarboxylate transporter isoform 4 (MCT4) and muscle buffering capacity were also measured.
RESULTS: Despite improvements in total work performed at CWR post-training, no differences were observed for TTF. The GPhos, HK, PFK, and LDH content and activity, and glycogen content also improved post-training only in the SIT group. Further, the MCT4 concentrations and muscle buffering capacity was also improved only for SIT group. However, no difference in glycogen depletion was observed between groups and time.
CONCLUSIONS: Five weeks of SIT improved the glycolytic pathway parameters and total work performed, however, glycogen depletion was not altered during CWR severe intensity exercise, and TTF remained similar.

DOI: https://doi.org/10.1249/MSS.0000000000003425
BMC Sports Sci Med Rehabil. 2024 Mar 22. 16(1): 70

Acute physiological responses and muscle recovery in females: a randomised controlled trial of muscle damaging exercise in hypoxia.

Erich Hohenauer, G Bianchi, V Wellauer, W Taube, R Clijsen.

   BACKGROUND: Studies have investigated the effects of training under hypoxia (HYP) after several weeks in a male population. However, there is still a lack of knowledge on the acute hypoxic effects on physiology and muscle recovery in a female population.
METHODS: This randomized-controlled trial aimed to investigate the acute effects of muscle damaging exercise, performed in HYP and normoxia (CON), on physiological responses and recovery characteristics in healthy females. Key inclusion criteria were recreationally active female participants between the age of 18 to 35 years without any previous surgeries and injuries, whilst key exclusion criteria were acute pain situations, pregnancy, and medication intake. The females conducted a muscle-damaging protocol, comprising 5 × 20 drop-jumps, in either HYP (FiO2: 12%) or CON (FiO2: 21%). Physiological responses, including capillary oxygenation (SpO2), muscle oxygenation (SmO2), heart rate (HR), core- (Tcore) and skin- (Tskin) temperature were assessed at the end of each exercise set. Recovery characteristics were quantified by taking venous blood samples (serum creatine-kinase [CK], C-reactive protein [CRP] and blood sedimentation rate [BSR]), assessing muscle swelling of the quadriceps femoris muscle, maximum voluntary isometric contraction (MVIC) of the knee extensor muscles, countermovement jump (CMJ) performance and muscle soreness ratings (DOMS) at 24-, 48- and 72-hrs post-exercise.
RESULTS: SpO2 (HYP: 76.7 ± 3.8%, CON: 95.5 ± 1.7%, p < 0.001) and SmO2 (HYP: 60.0 ± 9.3, CON: 73.4 ± 5.8%, p = 0.03) values were lower (p < 0.05) in HYP compared to CON at the end of the exercise-protocol. No physiological differences between HYP and CON were observed for HR, Tcore, and Tskin (all p > 0.05). There were also no differences detected for any recovery variable (CK, CRP, BSR, MVIC, CMJ, and DOMS) during the 72-hrs follow-up period between HYP and CON (all p > 0.05).
CONCLUSION: In conclusion, our results showed that muscle damaging exercise under HYP leads to reduced capillary and muscle oxygenation levels compared to normoxia with no difference in inflammatory response and muscle recovery during 72 h post-exercise.
TRIAL REGISTRATION: NCT04902924, May 26th 2021.

Keywords:  Exercise; Hypoxia; Muscle damage; Recovery; Training

DOI:  https://doi.org/10.1186/s13102-024-00861-1
Front Public Health. 2024 ;12 1289448

The effect of nutrition education sessions on energy availability, body composition, eating attitude and sports nutrition knowledge in young female endurance athletes.

Cansu Tektunalı Akman, Canan Gönen Aydın, Gülgün Ersoy.

  Nutrition knowledge plays a pivotal role in shaping dietary habits and food choices, particularly in the realm of sports nutrition. This study investigates the effects of a series of nutrition education sessions conducted by a registered dietitian on energy availability, various anthropometric measurements, eating attitudes, and sports nutrition knowledge in young female endurance athletes aged 15-18 years (football, basketball, volleyball) who engage in training for more than 10 h per week (n = 83). Participants were randomly divided into two groups with 45 individuals receiving six physical nutrition education lectures, and the remaining 38 participants receiving no nutrition education. Participants completed the low energy availability in females questionnaire (LEAF-Q), Eating Attitude Test (EAT-26), and Sports Nutrition Knowledge Questionnaire (SNKQ). Energy and nutrient intakes were evaluated through 3-day food records, while exercise energy expenditure was assessed using 3-day activity logs. All of the questionnaires were repeated after 6 months. At baseline, the prevalence of LEA among athletes was determined to be 63.8%. In the intervention group, energy availability (EA) and SNKQ scores increased, and LEAF-Q scores decreased significantly (p < 0.05). However, there was no significant change in EAT-26 scores between the two groups. Energy intake, weight, fat-free mass, and resting metabolic rate have been increased significantly in the intervention group (p < 0,05). These findings suggest that nutrition education proves beneficial in enhancing dietary intake, positively influencing body composition, and improving nutrition knowledge, ultimately contributing to increased energy availability in female athletes over the short term.

Keywords:  body composition; eating attitude; low energy availability; nutrition education; sports nutrition knowledge; young female athletes

DOI:  https://doi.org/10.3389/fpubh.2024.1289448
Nutrients. 2024 Mar 20. pii: 896. [Epub ahead of print]16(6):

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Shota Yamaguchi, Takayuki Inami, Hiroyuki Ishida, Akihisa Morito, Satoshi Yamada, Naoya Nagata, Mitsuyoshi Murayama.

  Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments. The creatine (CRE) and placebo (PLA) groups ingested creatine and crystalline cellulose, respectively, for 28 days. They subsequently performed dumbbell exercises while emphasizing eccentric contraction of the elbow flexors. The EIMD was evaluated before and after exercise. The range of motion was significantly higher in the CRE group than in the PLA group 24 h (h) post exercise. A similar difference was detected in maximum voluntary contraction at 0, 48, 96, and 168 h post exercise (p = 0.017-0.047). The upper arm circumference was significantly lower in the CRE group than in the PLA group at 48, 72, 96, and 168 h post exercise (p = 0.002-0.030). Similar variation was observed in the shear modulus of the biceps brachii muscle at 96 and 168 h post exercise (p = 0.003-0.021) and in muscle fatigue at 0 and 168 h post exercise (p = 0.012-0.032). These findings demonstrate CrM-mediated accelerated recovery from EIMD, suggesting that CrM is an effective supplement for EIMD recovery.

Keywords:  creatine monohydrate; dietary supplementation; eccentric exercise; exercise-induced muscle damage

DOI:  https://doi.org/10.3390/nu16060896
Biomolecules. 2024 Feb 22. pii: 260. [Epub ahead of print]14(3):

Tricarboxylic Acid Cycle Intermediates and Individual Ageing.

Natalia Kurhaluk.

  Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm Caenorhabditis elegans, Drosophila, mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.

Keywords:  ageing mechanisms; anti-ageing therapy; bioenergetic mechanisms of ageing; individual ageing processes; individual physiological reactivity; tricarboxylic acid cycle intermediates

DOI:  https://doi.org/10.3390/biom14030260
Cells. 2024 Mar 11. pii: 486. [Epub ahead of print]13(6):

Cannabidiol Disrupts Mitochondrial Respiration and Metabolism and Dysregulates Trophoblast Cell Differentiation.

Tina Podinic, Louise Limoges, Cristina Monaco, Andie MacAndrew, Mahek Minhas, Joshua Nederveen, Sandeep Raha.

  Trophoblast differentiation is a crucial process in the formation of the placenta where cytotrophoblasts (CTs) differentiate and fuse to form the syncytiotrophoblast (ST). The bioactive components of cannabis, such as Δ9-THC, are known to disrupt trophoblast differentiation and fusion, as well as mitochondrial dynamics and respiration. However, less is known about the impact of cannabidiol (CBD) on trophoblast differentiation. Due to the central role of mitochondria in stem cell differentiation, we evaluated the impact of CBD on trophoblast mitochondrial function and differentiation. Using BeWo b30 cells, we observed decreased levels of mRNA for markers of syncytialization (GCM1, ERVW1, hCG) following 20 µM CBD treatment during differentiation. In CTs, CBD elevated transcript levels for the mitochondrial and cellular stress markers HSP60 and HSP70, respectively. Furthermore, CBD treatment also increased the lipid peroxidation and oxidative damage marker 4-hydroxynonenal. Mitochondrial membrane potential, basal respiration and ATP production were diminished with the 20 µM CBD treatment in both sub-lineages. mRNA levels for endocannabinoid system (ECS) components (FAAH, NAPEPLD, TRPV1, CB1, CB2, PPARγ) were altered differentially by CBD in CTs and STs. Overall, we demonstrate that CBD impairs trophoblast differentiation and fusion, as well as mitochondrial bioenergetics and redox homeostasis.

Keywords:  cannabis; cytotrophoblast; differentiation; endocannabinoid system; mitochondria; oxidative stress; placentation; pregnancy; syncytiotrophoblast; trophoblast

DOI:  https://doi.org/10.3390/cells13060486
Metabolites. 2024 Mar 17. pii: 167. [Epub ahead of print]14(3):

Resting Metabolic Rate and Substrate Utilization during Energy and Protein Availability in Male and Female Athletes.

Mahmoud M A Abulmeaty, Ali Almajwal, Mervat Elsayed, Heba Hassan, Thamer Alsager, Zaid Aldossari.

  Active athletes frequently develop low energy (LEA) and protein availabilities (LPA) with consequent changes in the vital metabolic processes, especially resting metabolic rate (RMR) and substrate utilization. This study investigated the association of energy and protein intakes with RMR and substrate utilization in male and female athletes and those with LEA and LPA. Sixty athletes (35% female, 26.83 ± 7.12 y) were enrolled in this study. Anthropometric measurements and body composition analysis were reported to estimate fat-free mass (eFFM). Dietary intakes were recorded by two-day multiple-pass 24 h recall records and three-day food records and then analyzed by food processor software to calculate protein intake (PI) and energy intake (EI). Indirect calorimetry was used to measure RMR and percentages of substrate utilization. Activity-energy expenditure (AEE) was assessed by using an Actighrphy sensor for three days. Energy availability was calculated using the following formula (EA = EI - AEE/eFFM). The correlation of EI and PI with RMR and substrate utilization was tested with Pearson correlation. In the LEA group, both EI and PI correlated positively with RMR (r = 0.308, 0.355, respectively, p < 0.05). In addition, EI showed a positive correlation with the percentage of fat utilization. In the male and sufficient-PA groups, PI correlated positively with the RMR and negatively with the percentage of protein utilization. In conclusion, the percentage of LEA is markedly prevalent in our sample, with a higher prevalence among males. Athletes with LEA had lower fat utilization and lower RMR, while those with sufficient PA showed lower protein utilization with excessive PI. These findings may explain the metabolic responses in the cases of LEA and LPA.

Keywords:  RMR; athletes; energy availability; protein availability; substrate utilization

DOI:  https://doi.org/10.3390/metabo14030167
Biomolecules. 2024 Feb 26. pii: 281. [Epub ahead of print]14(3):

Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Sandra Almeida-Reis, Alexandra Carvalho, Conceição Dias, Raquel Brito, Rita Silva, Teresa Almeida-Santos, João Ramalho-Santos, Ana Paula Sousa.

  Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.

Keywords:  ATP synthase; cumulus cells; maternal aging; mitochondria; oxidative phosphorylation

DOI:  https://doi.org/10.3390/biom14030281
J Cell Physiol. 2024 Mar 26.

Maternal Ezh1/2 deficiency impairs the function of mitochondria in mouse oocytes and early embryos.

Dan Zhang, Wenbo Deng, Ting Jiang, Yinan Zhao, Dandan Bai, Yingpu Tian, Shuangbo Kong, Leilei Zhang, Haibin Wang, Shaorong Gao, Zhongxian Lu.

  Maternal histone methyltransferase is critical for epigenetic regulation and development of mammalian embryos by regulating histone and DNA modifications. Here, we reported a novel mechanism by revealing the critical effects of maternal Ezh1/2 deletion on mitochondria in MII oocytes and early embryos in mice. We found that Ezh1/2 knockout in mouse MII oocytes impaired the structure of mitochondria and decreased its number, but membrane potential and respiratory function of mitochondrion were increased. The similar effects of Ezh1/2 deletion have been observed in 2-cell and morula embryos, indicating that the effects of maternal Ezh1/2 deficiency on mitochondrion extend to early embryos. However, the loss of maternal Ezh1/2 resulted in a severe defect of morula: the number, membrane potential, respiratory function, and ATP production of mitochondrion dropped significantly. Content of reactive oxygen species was raised in both MII oocytes and early embryos, suggesting maternal Ezh1/2 knockout induced oxidative stress. In addition, maternal Ezh1/2 ablation interfered the autophagy in morula and blastocyst embryos. Finally, maternal Ezh1/2 deletion led to cell apoptosis in blastocyst embryos in mice. By analyzing the gene expression profile, we revealed that maternal Ezh1/2 knockout affected the expression of mitochondrial related genes in MII oocytes and early embryos. The chromatin immunoprecipitation-polymerase chain reaction assay demonstrated that Ezh1/2 directly regulated the expression of genes Fxyd6, Adpgk, Aurkb, Zfp521, Ehd3, Sgms2, Pygl, Slc1a1, and Chst12 by H3K27me3 modification. In conclusion, our study revealed the critical effect of maternal Ezh1/2 on the structure and function of mitochondria in oocytes and early embryos, and suggested a novel mechanism underlying maternal epigenetic regulation on early embryonic development through the modulation of mitochondrial status.

Keywords:  Ezh1; Ezh2; embryonic development

DOI:  https://doi.org/10.1002/jcp.31244
Sports (Basel). 2024 Mar 14. pii: 82. [Epub ahead of print]12(3):

The Effect of Oral Adenosine Triphosphate (ATP) Supplementation on Anaerobic Exercise in Healthy Resistance-Trained Individuals: A Systematic Review and Meta-Analysis.

Roberto González-Marenco, Ivonne Azeret Estrada-Sánchez, Martha Medina-Escobedo, Rodolfo Chim-Aké, Roberto Lugo.

  Adenosine triphosphate (ATP) is an energy and signaling molecule. It is synthesized endogenously and can be taken as an oral supplement. This review aimed to identify the effects of oral ATP supplementation on anaerobic exercise in healthy resistance-trained adults. A systematic review and meta-analysis were performed based on the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) criteria. The inclusion criteria were articles published from 2000 to 2022, with anaerobic variables (maximal strength, maximum repetitions, and maximum anaerobic power) measurable in healthy adults with experience in resistance training, only randomized placebo-controlled clinical trials (RCTs), and with the acute (a single dose 30 min to 24 h before the tests) and/or chronic (>1 day) oral supplementation of ATP. A total of five RCTs with 121 adult men were included. The oral ATP supplementation achieved significantly greater gains in maximal strength compared with the placebo (PL) (MD = 8.13 kg, 95%CI [3.36-12.90], p < 0.001). Still, no differences were observed in the maximum number of repetitions or the maximum anaerobic power. Furthermore, 400 mg of ATP showed improvement in anaerobic exercise regardless of the duration of the supplementation protocol. In conclusion, supplementation with 400 mg of ATP doses can improve maximal muscle strength in resistance-trained men.

Keywords:  adenosine triphosphate; dietary supplements; muscle strength; performance-enhancing substances; resistance training

DOI:  https://doi.org/10.3390/sports12030082
Front Biosci (Landmark Ed). 2024 Mar 13. 29(3): 99

The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium.

Erna Mitaishvili, Hanna Feinsod, Zachary David, Jessica Shpigel, Chelsea Fernandez, Moira Sauane, Columba de la Parra.

  Altered metabolism represents a fundamental difference between cancer cells and normal cells. Cancer cells have a unique ability to reprogram their metabolism by deviating their reliance from primarily oxidative phosphorylation (OXPHOS) to glycolysis, in order to support their survival. This metabolic phenotype is referred to as the "Warburg effect" and is associated with an increase in glucose uptake, and a diversion of glycolytic intermediates to alternative pathways that support anabolic processes. These processes include synthesis of nucleic acids, lipids, and proteins, necessary for the rapidly dividing cancer cells, sustaining their growth, proliferation, and capacity for successful metastasis. Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with the poorest patient outcome due to its high rate of metastasis. TNBC is characterized by elevated glycolysis and in certain instances, low OXPHOS. This metabolic dysregulation is linked to chemotherapeutic resistance in TNBC research models and patient samples. There is more than a single mechanism by which this metabolic switch occurs and here, we review the current knowledge of relevant molecular mechanisms involved in advanced breast cancer metabolism, focusing on TNBC. These mechanisms include the Warburg effect, glycolytic adaptations, microRNA regulation, mitochondrial involvement, mitochondrial calcium signaling, and a more recent player in metabolic regulation, JAK/STAT signaling. In addition, we explore some of the drugs and compounds targeting cancer metabolic reprogramming. Research on these mechanisms is highly promising and could ultimately offer new opportunities for the development of innovative therapies to treat advanced breast cancer characterized by dysregulated metabolism.

Keywords:  JAK/STAT; OXPHOS; ROS; TNBC; Warburg effect; glycolysis; hexokinase; metabolic reprogramming; miRNAs; mitochondrial Ca2+

DOI:  https://doi.org/10.31083/j.fbl2903099
J Ovarian Res. 2024 Mar 27. 17(1): 69

Role of polyphenols in remodeling the host gut microbiota in polycystic ovary syndrome.

Ping Zhou, Penghui Feng, Baoying Liao, Lin Fu, Hongying Shan, Canhui Cao, Renxin Luo, Tianliu Peng, Fenting Liu, Rong Li.

  Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.

Keywords:  Anthocyanins; Green tea catechins; Gut microbiota; Polycystic ovary syndrome; Polyphenols

DOI:  https://doi.org/10.1186/s13048-024-01354-y
Mol Cell Endocrinol. 2024 Mar 27. pii: S0303-7207(24)00055-8. [Epub ahead of print] 112199

Insulin signaling and mitochondrial phenotype of skeletal muscle are programmed in utero by maternal diabetes.

Eduardo Klöppel, Larissa L Cruz, Laura F L Prado-Souza, Adam Eckhardt, José E Corrente, Daniela C Dos Santos, Luís A Justulin, Tiago Rodrigues, Gustavo T Volpato, Débora C Damasceno.

  Maternal diabetes may influence glucose metabolism in adult offspring, an area with limited research on underlying mechanisms. Our study explored the impact of maternal hyperglycemia during pregnancy on insulin resistance development. Adult female Sprague-Dawley rats from control and diabetic mothers were mated, and their female offspring were monitored for 150 days. The rats were euthanized for blood and muscle samples. Maternal diabetes led to heightened insulin levels, increased HOMA-IR, elevated triglycerides, and a raised TyG index in adult offspring. Muscle samples showed a decreased protein expression of AMPK, PI3K, MAPK, DRP1, and MFF. These changes induced intergenerational metabolic programming in female pups, resulting in insulin resistance, dyslipidemia, and glucose intolerance by day 150. Findings highlight the offspring's adaptation to maternal hyperglycemia, involving insulin resistance, metabolic alterations, the downregulation of insulin signaling sensors, and disturbed mitochondrial morphology. Maintaining maternal glycemic control emerges as crucial in mitigating diabetes-associated disorders in adult offspring.

Keywords:  Fetal programming; Hyperglycemia; Insulin resistance; Mitochondria; Rat; Skeletal muscle

DOI:  https://doi.org/10.1016/j.mce.2024.112199