bims-mifefi 2024-04-07 papers

Issue of 2024–04–07
five papers selected by
Kayla Vandiver, East Carolina University

Physiol Rep. 2024 Apr;12(7): e15987

Exercise increases TCA intermediate concentrations during low-calorie diet independent of insulin resistance among women with obesity.

Tristan J Ragland, Steven K Malin.

Tricarboxylic acid cycle intermediates (TCAi) have been proposed to act as myokines that influence energy metabolism. We determined if 2-weeks of low-calorie diet with interval exercise (LCD + INT) would increase TCAi more than a low-calorie diet (LCD). Twenty-three women were randomized to 2-weeks of LCD (n = 12, 48.4 ± 2.5 years, 37.8 ± 1.5 kg/m2, ~1200 kcal/d) or LCD + INT (n = 11, 47.6 ± 4.3 years, 37.9 ± 2.3 kg/m2; 60 min/d supervised INT of 3 min 90% & 50% HRpeak). TCAi and amino acids (AA) were measured at 0 min of a 75 g OGTT, while glucose, insulin, and FFA were obtained at 0, 30, 60, 90, 120, and 180 min to assess total area under the curve (tAUC180min) and insulin resistance (IR; tAUC180min of Glucose × Insulin). Fuel use (indirect calorimetry) was also collected at 0, 60, 120, and 180 min as was fitness (VO2peak) and body composition (BodPod). Treatments reduced weight (p < 0.001), fasting RER (p = 0.01), and IR (p = 0.03), although LCD + INT increased VO2peak (p = 0.02) and maintained RER tAUC180min (p = 0.05) versus LCD. Treatments increased FFA tAUC180min (p = 0.005), cis-aconitate, isocitrate, and succinate (p ≤ 0.02), as well as reduced phenylalanine and tryptophan, cysteine (p ≤ 0.005). However, LCD + INT increased malate, citrate, α-ketoglutarate, and alanine more than LCD (p ≤ 0.04). Thus, INT enhanced LCD effects on some TCAi in women with obesity independent of IR.

Keywords: amino acids; diabetes; interval training; obesity; tricarboxylic acid cycle

DOI: https://doi.org/10.14814/phy2.15987

Free Radic Biol Med. 2024 Apr 02. pii: S0891-5849(24)00170-9. [Epub ahead of print]

Mitochondrial remodeling underlying age-induced skeletal muscle wasting: let's talk about sex.

Alexandra Moreira-Pais, Rui Vitorino, Cláudia Sousa-Mendes, Maria João Neuparth, Alessandro Nuccio, Claudio Luparello, Alessandro Attanzio, Petr Novák, Dmitry Loginov, Rita Nogueira-Ferreira, Adelino Leite-Moreira, Paula A Oliveira, Rita Ferreira, José A Duarte.

Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics.

Keywords: Fatty acid oxidation; Mitophagy; Oxidative phosphorylation; Sarcopenia; Sexual dimorphism

DOI: https://doi.org/10.1016/j.freeradbiomed.2024.04.005

Endocrinology. 2024 Apr 02. pii: bqae036. [Epub ahead of print]

Hormonal basis of biological sex differences in human athletic performance.

Jonathon W Senefeld, Sandra K Hunter.

Biological sex is a primary determinant of athletic human performance involving strength, power, speed, and aerobic endurance and is more predictive of athletic performance than gender. This perspective article highlights three key medical and physiological insights related to recent evolving research into the sex differences in human physical performance: (1) sex and gender are not the same; (2) males and females exhibit profound differences in physical performance with males outperforming females in events and sports involving strength, power, speed and aerobic endurance; (3) endogenous testosterone underpins sex differences in human physical performance with questions remaining on the roles of minipuberty in the sex differences in performance in prepubescent youth and the presence of the Y chromosome (SRY gene expression) in males, on athletic performance across all ages. Last, females are underrepresented as participants in biomedical research which has led to an historical dearth of information on the mechanisms for sex differences in human physical performance and the capabilities of the female body. Collectively, greater effort and resources are needed to address the hormonal mechanisms for biological sex differences in human athletic performance before and after puberty.

Keywords: athletics; gender; physical performance; sex; sex chromosomes; testosterone

DOI: https://doi.org/10.1210/endocr/bqae036

J Muscle Res Cell Motil. 2024 Apr 05.

Skeletal muscle of young females under resistance exercise exhibits a unique innate immune cell infiltration profile compared to males and elderly individuals.

Paola Castrogiovanni, Cristina Sanfilippo, Rosa Imbesi, Giacomo Lazzarino, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti, Lazzarino Giuseppe, Ignazio Barbagallo, Amer M Alanazi, Michele Vecchio, Francesco Cappello, Giuseppe Musumeci, Michelino Di Rosa.

Muscle damage resulting from physical activities such as exercise triggers an immune response crucial for tissue repair and recovery. This study investigates the immune cell profiles in muscle biopsies of individuals engaged in resistance exercise (RE) and explores the impact of age and sex on the immune response following exercise-induced muscle damage. Microarray datasets from muscle biopsies of young and old subjects were analyzed, focusing on the gene expression patterns associated with immune cell activation. Genes were compared with immune cell signatures to reveal the cellular landscape during exercise. Results show that the most significant modulated gene after RE was Folliculin Interacting Protein 2 (FNIP2) a crucial regulator in cellular homeostasis. Moreover, the transcriptome was stratified based on the expression of FNIP2 and the 203 genes common to the groups obtained based on sex and age. Gene ontology analysis highlighted the FLCN-FNIP1-FNIP2 complex, which exerts as a negative feedback loop to Pi3k-Akt-mTORC1 pathway. Furthermore, we highlighted that the young females exhibit a distinct innate immune cell activation signature compared to males after a RE session. Specifically, young females demonstrate a notable overlap with dendritic cells (DCs), M1 macrophages, M2 macrophages, and neutrophils, while young males overlap with M1 macrophages, M2 macrophages, and motor neurons. Interestingly, in elderly subjects, both sexes display M1 macrophage activation signatures. Comparison of young and elderly signatures reveals an increased M1 macrophage percentage in young subjects. Additionally, common genes were identified in both sexes across different age groups, elucidating biological functions related to cell remodeling and immune activation. This study underscores the intricate interplay between sex, age, and the immune response in muscle tissue following RE, offering potential directions for future research. Nevertheless, there is a need for further studies to delve deeper and confirm the dynamics of immune cells in response to exercise-induced muscle damage.

Keywords: Bioinformatics; Deconvolution; Dendritic cells; Macrophages; Muscle biopsies

DOI: https://doi.org/10.1007/s10974-024-09668-6

Biofactors. 2024 Apr 04.

Myokines: A central point in managing redox homeostasis and quality of life.

Richa Rathor, Geetha Suryakumar.

Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle-secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life.

Keywords: adipose tissue; bone; brain; cross‐talk; muscle; myokine; redox homeostasis

DOI: https://doi.org/10.1002/biof.2054