Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function

Montero, David; Madsen, Klavs; Meinild‐Lundby, Anne‐Kristine; Edin, Fredrik; Lundby, Carsten

doi:10.1113/ep087007

Cited by 83 publications

(87 citation statements)

References 52 publications

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“…In aggregate, the current literature suggests inherent differences between males and females on both mitochondrial content and function [165,[167][168][169][170]. These differences may at least partially contribute to differential mitochondrial alterations during muscle pathologies and subsequent muscle loss [35,46,171].…”

Section: Mitochondria and Sex Hormonesmentioning

confidence: 96%

“…Mitochondrial quality has been a recently proposed mediator of muscle size and function [108]. Females in general tend to preferentially oxidize fat as the primary energy substrate [34,165,166], aligning with a greater relative content of type I fibers [35,36]. Therefore, suggesting females' higher reliance on mitochondrial oxidative phosphorylation for ATP synthesis.…”

Section: Mitochondrial Differences Between Males and Femalesmentioning

confidence: 99%

“…To date, multiple studies have found mitochondrial function, morphology, and content to differ between males and females. Indeed, animal and human studies across multiple tissues have found higher mitochondrial content per gram of tissue and greater transcription factors associated with mitochondrial biogenesis in females compared to males [165,[167][168][169][170]. Female gastrocnemius muscles have greater mitochondrial content and mtDNA per gram of tissue compared to males as well as more ATP synthase, TFAM protein, and mitochondrial complexes [168].…”

Section: Mitochondrial Differences Between Males and Femalesmentioning

confidence: 99%

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Muscle metabolism and atrophy: let’s talk about sex

2019

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Skeletal muscle health is a strong predictor of overall health and longevity. Pathologies affecting skeletal muscle such as cancer cachexia, intensive care unit treatment, muscular dystrophies, and others are associated with decreased quality of life and increased mortality. Recent research has begun to determine that these muscular pathologies appear to present and develop differently between males and females. However, to our knowledge, there has yet to be a comprehensive review on musculoskeletal differences between males and females and how these differences may contribute to sex differences in muscle pathologies. Herein, we present a review of the current literature on muscle phenotype and physiology between males and females and how these differences may contribute to differential responses to atrophic stimuli. In general, females appear to be more susceptible to disuse induced muscle wasting, yet protected from inflammation induced (such as cancer cachexia) muscle wasting compared to males. These differences may be due in part to differences in muscle protein turnover, satellite cell content and proliferation, hormonal interactions, and mitochondrial differences between males and females. However, more works specifically examining muscle pathologies in females are necessary to more fully understand the inherent sex-based differences in muscle pathologies between the sexes and how they may correspond to different clinical treatments.

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Section: Mitochondria and Sex Hormonesmentioning

confidence: 96%

Section: Mitochondrial Differences Between Males and Femalesmentioning

confidence: 99%

Section: Mitochondrial Differences Between Males and Femalesmentioning

confidence: 99%

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Muscle metabolism and atrophy: let’s talk about sex

2019

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“…Since the pioneering work of John Holloszy in the 1960's, it has been known that exercise training can increase mitochondrial content (as assessed by total protein content of the mitochondria) (84). Subsequent research using transmission electron microscopy (TEM), considered the 'gold standard' for the measurement of mitochondrial content (102), has confirmed these results in humans (40,52,57,81,90,91,106,113,124,126). However, while TEM can provide measures of mitochondrial content, and also size and shape, it requires specialized equipment and expertise not available in all laboratories.…”

Section: B) Mitochondrial Contentmentioning

confidence: 96%

High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions

et al. 2019

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It is well established that different types of exercise can provide a powerful stimulus for mitochondrial biogenesis. However, there are conflicting findings in the literature, and a consensus has not been reached regarding the efficacy of high-intensity exercise to promote mitochondrial biogenesis in humans. The purpose of this review is to examine current controversies in the field and to highlight some important methodological issues that need to be addressed to resolve existing conflicts.

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“…Thus, it could be clinically relevant to identify what sex-specific factors permit females to overcome the potentially harmful effect of the m.1382A>C polymorphism on T2D seen in sedentary men. These may include sex-specific variation in mitochondrial mass or function or direct effects of sex-steroids on mitochondrial biology that favor females 36 .…”

Section: Discussionmentioning

confidence: 99%

A Pro-Diabetogenic mtDNA Polymorphism in the Mitochondrial-Derived Peptide, MOTS-c

Zempo

Kim

Fuku

et al. 2019

Preprint

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49Type 2 Diabetes (T2D) is an emerging public health problem in Asia. An Asian mitochondrial DNA 50 variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an 51 insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n=27,527, J-52 MICC, MEC, and TMM) showed that males but not females with the C-allele exhibit a higher 53 prevalence of T2D. Furthermore, in J-MICC, only males with the C-allele in the lowest tertile of 54 physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. 55High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose 56 tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. 57Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the 58 m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with 59 exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c. 60 61 64 65The prevalence of type 2 diabetes mellitus (T2D) is growing dramatically. Over 400 million 66 individuals were diagnosed with T2D worldwide in 2015, and the International Diabetes Federation 67 projects that at least 600 million people will need to be treated for T2D by 2040 1 . However, treating 68 T2D is challenging because the disease etiology is genetically heterogeneous and varies among 69 ethnicities 2-4 . For example, a recent meta-analysis showed that T2D is 72% heritable (95% CI: 61-70 78%) 2 , and the Western Pacific Region -including China and Japan -makes up ~37% of the total 71 T2D diagnoses in the world 1 . This is particularly noteworthy because although East-Asian 72 populations have lower mean body mass index (BMI) than Caucasian populations, they have a 73 higher susceptibility to T2D compared to Caucasians 5 . Furthermore, when matched for BMI, East 74Asians have a greater percentage of body fat and a tendency for increased visceral adiposity 6 . 75T2D in Asian patients is characterized by early beta cell dysfunction, in contrast to Caucasian 76 populations that have more insulin resistance 7,8 . Thus, ethnicity-based DNA variations likely 77 influence the pathogenesis of T2D. 78While diabetes directly caused by mutations in mtDNA are extremely rare 9 , several genetic 79 analyses revealed that mtDNA polymorphisms contribute to T2D risk in both European and Asian 80 populations 10,11 . Notably, mtDNA sequences are more varied by ethnicity compared to nuclear 81 DNA sequences due to the 10-times higher mutation rate of mtDNA compared to nuclear DNA 82 12,13 . As a result, certain mtDNA polymorphisms could contribute to the T2D prevalence in different 83 ethnicities. The human mitochondrial genome consists of 16,569-base pairs and encodes 37 84 genes including 13 full size proteins involved in oxidative phosphorylation, 2 rRNA, and 22 tRNA 85 genes that are necessary for protein synthesis within the mitochondria. Genetic polymorphisms in 86 t...

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Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function

Cited by 83 publications

References 52 publications

Muscle metabolism and atrophy: let’s talk about sex

Muscle metabolism and atrophy: let’s talk about sex

High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions

A Pro-Diabetogenic mtDNA Polymorphism in the Mitochondrial-Derived Peptide, MOTS-c

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