bims-exemet 2021-04-25 papers

Issue of 2021–04–25
five papers selected by
Javier Botella Ruiz, Victoria University

Physiol Genomics. 2021 Apr 19.

Muscle Transcriptional Networks Linked to Resistance Exercise Training Hypertrophic Response Heterogeneity.

Kaleen M Lavin, Margaret B Bell, Jeremy S McAdam, Bailey D Peck, R Grace Walton, Samuel T Windham, S Craig Tuggle, Douglas E Long, Phillip A Kern, Charlotte A Peterson, Marcas M Bamman.

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as (i) predictive of hypertrophy, (ii) responsive to RT independent of muscle hypertrophy, or (iii) plastic with hypertrophy. Older adults (n=31, 18F/13M, 70±4y) underwent 14-wk RT (3d/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed by pre- to post-RT change in mid-thigh muscle cross-sectional area (CSA) [computed tomography (CT), primary outcome], and thigh lean mass [dual-energy x-ray absorptiometry (DXA), secondary outcome]. Transcriptome-wide poly-A RNA-seq was performed on vastus lateralis tissue collected pre- (n=31) and post-RT (n=22). Prediction networks (using only baseline RNAseq) were identified by Weighted Gene Correlation Network Analysis (WGCNA). To identify Plasticity networks, WGCNA change indices for paired samples were calculated and correlated to changes in muscle size outcomes. Pathway-Level Information ExtractoR (PLIER) was applied to identify Response networks and link genes to biological annotation. Predictionnetworks (n=6) confirmed transcripts previously connected to resistance/ aerobic training adaptations in the MetaMEx database while revealing novel member genes that should fuel future research to understand the influence of baseline muscle gene expression on hypertrophy. Response networks (n=6) indicated RT-induced increase in aerobic metabolism and reduced expression of genes associated with spliceosome biology and type-I myofibers. A single exploratory Plasticity network was identified. Findings support that inter-individual differences in baseline gene expression may contribute more than RT-induced changes in gene networks to muscle hypertrophic response heterogeneity.

Keywords: RNA-seq; muscle growth; network biology; resistance exercise; skeletal muscle

DOI: https://doi.org/10.1152/physiolgenomics.00154.2020

Cell Rep. 2021 Apr 20. pii: S2211-1247(21)00332-6. [Epub ahead of print]35(3): 109018

Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity.

Rodrigo W Alves de Souza, David Gallo, Ghee Rye Lee, Eri Katsuyama, Alexa Schaufler, Janick Weber, Eva Csizmadia, George C Tsokos, Lauren G Koch, Steven L Britton, Ulrik Wisløff, Patricia C Brum, Leo E Otterbein.

Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.

Keywords: DAMP; exercise training; heme; heme oxygenase-1; hemopexin; mitochondrial dysfunction; muscle atrophy; muscle microtrauma; satellite cells

DOI: https://doi.org/10.1016/j.celrep.2021.109018

FASEB J. 2021 May;35(5): e21587

An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.

Christopher G Vann, Robert W Morton, Christopher B Mobley, Ivan J Vechetti, Brian K Ferguson, Cody T Haun, Shelby C Osburn, Casey L Sexton, Carlton D Fox, Matthew A Romero, Paul A Roberson, Sara Y Oikawa, Chris McGlory, Kaelin C Young, John J McCarthy, Stuart M Phillips, Michael D Roberts.

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.

Keywords: GLI3; hypertrophy; polymorphisms; skeletal muscle

DOI: https://doi.org/10.1096/fj.202100113RR

Sci Rep. 2021 Apr 21. 11(1): 8574

Resistance exercise training improves glucose homeostasis by enhancing insulin secretion in C57BL/6 mice.

Gabriela Alves Bronczek, Gabriela Moreira Soares, Jaqueline Fernandes de Barros, Jean Franciesco Vettorazzi, Mirian Ayumi Kurauti, Emílio Marconato-Júnior, Lucas Zangerolamo, Carine Marmentini, Antonio Carlos Boschero, José Maria Costa-Júnior.

Resistance exercise exerts beneficial effects on glycemic control, which could be mediated by exercise-induced humoral factors released in the bloodstream. Here, we used C57Bl/6 healthy mice, submitted to resistance exercise training for 10 weeks. Trained mice presented higher muscle weight and maximum voluntary carrying capacity, combined with reduced body weight gain and fat deposition. Resistance training improved glucose tolerance and reduced glycemia, with no alterations in insulin sensitivity. In addition, trained mice displayed higher insulinemia in fed state, associated with increased glucose-stimulated insulin secretion. Islets from trained mice showed reduced expression of genes related to endoplasmic reticulum (ER) stress, associated with increased expression of Ins2. INS-1E beta-cells incubated with serum from trained mice displayed similar pattern of insulin secretion and gene expression than isolated islets from trained mice. When exposed to CPA (an ER stress inducer), the serum from trained mice partially preserved the secretory function of INS-1E cells, and prevented CPA-induced apoptosis. These data suggest that resistance training, in healthy mice, improves glucose homeostasis by enhancing insulin secretion, which could be driven, at least in part, by humoral factors.

DOI: https://doi.org/10.1038/s41598-021-88105-x

Endocrines. 2021 Jun;2(2): 65-78

Exercise as a Therapeutic Intervention in Gestational Diabetes Mellitus.

Konstantina Dipla, Andreas Zafeiridis, Gesthimani Mintziori, Afroditi K Boutou, Dimitrios G Goulis, Anthony C Hackney.

Gestational Diabetes Mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Regular exercise is important for a healthy pregnancy and can lower the risk of developing GDM. For women with GDM, exercise is safe and can affect the pregnancy outcomes beneficially. A single exercise bout increases skeletal muscle glucose uptake, minimizing hyperglycemia. Regular exercise training promotes mitochondrial biogenesis, improves oxidative capacity, enhances insulin sensitivity and vascular function, and reduces systemic inflammation. Exercise may also aid in lowering the insulin dose in insulin-treated pregnant women. Despite these benefits, women with GDM are usually inactive or have poor participation in exercise training. Attractive individualized exercise programs that will increase adherence and result in optimal maternal and offspring benefits are needed. However, as women with GDM have a unique physiology, more attention is required during exercise prescription. This review (i) summarizes the cardiovascular and metabolic adaptations due to pregnancy and outlines the mechanisms through which exercise can improve glycemic control and overall health in insulin resistance states, (ii) presents the pathophysiological alterations induced by GDM that affect exercise responses, and (iii) highlights cardinal points of an exercise program for women with GDM.

Keywords: diabetes; exercise; exercise endocrinology; exercise physiology; hormones; pregnancy; pregnancy endocrinology; women’s health

DOI: https://doi.org/10.3390/endocrines2020007