Hypoxia-Induced Cardiopulmonary Remodeling and Recovery: Critical Roles of the Proximal Pulmonary Artery, Macrophages, and Exercise DOI Open Access
Abhay B. Ramachandra, Prapti Sharma, Ruben De Man

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Abstract Hypoxemia impairs cardiopulmonary function. We investigated pulmonary artery remodeling in mice exposed to chronic hypoxia for up five weeks and quantified associated changes cardiac lung function, without or with subsequent normoxic recovery the absence presence of exercise pharmacological intervention. Hypoxia-induced stiffening proximal stemmed primarily from adventitial collagen, which resulted part altered inter-cellular signaling phenotypic mural smooth muscle cells macrophages. Such appeared precede associate both right ventricular dysfunction, emerging similar degrees regardless age onset during postnatal development. Key homeostatic target values wall mechanics were recovered by arteries while other only partially. Overall dysfunction due was similarly partially reversible. Remodeling system is a complex, multi-scale process that involves maladaptations artery.

Language: Английский

The mitochondrial multi-omic response to exercise training across rat tissues DOI Creative Commons
David Amar, Nicole R. Gay, David Jimenez‐Morales

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(6), P. 1411 - 1429.e10

Published: May 2, 2024

Language: Английский

Citations

19
Molecular control of endurance training adaptation in male mouse skeletal muscle DOI Creative Commons
Regula Furrer, Barbara Heim, Svenia Schmid

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(11), P. 2020 - 2035

Published: Sept. 11, 2023

Abstract Skeletal muscle has an enormous plastic potential to adapt various external and internal perturbations. Although morphological changes in endurance-trained muscles are well described, the molecular underpinnings of training adaptation poorly understood. We therefore aimed elucidate signature trained male mice unravel status-dependent responses acute bout exercise. Our results reveal that, even though at baseline unexpectedly low number genes define muscle, status substantially affects transcriptional response challenge, both quantitatively qualitatively, part associated with epigenetic modifications. Finally, transiently activated factors such as peroxisome proliferator-activated receptor-γ coactivator 1α indispensable for normal adaptation. Together, these provide a framework temporal exercise that underpins plasticity training.

Language: Английский

Citations

32
Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures DOI Creative Commons
Venugopalan D. Nair, Hanna Pinças, Gregory R. Smith

et al.

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(6), P. 100421 - 100421

Published: May 1, 2024

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, RNA-seq datasets from eight control endurance exercise-trained (EET) rats. Integration of baseline mapped gene location dependence epigenetic features identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks EET showed little overlap predominantly comprised tissue-type enriched genes. We sex differences transcriptomic epigenomic changes induced by EET. However, sex-biased were linked shared signaling pathways. found that G protein-coupled receptor-encoding genes are regulated EET, suggesting a role for these receptors adaptations training tissues. Our findings provide new insights into underlying EET-induced benefits organs.

Language: Английский

Citations

14
Physiological Adaptations to Progressive Endurance Exercise Training in Adult And Aged Rats: Insights from The Molecular Transducers of Physical Activity Consortium (MoTrPAC) DOI Creative Commons
Simon Schenk, Tyler J. Sagendorf, Gina M. Many

et al.

Function, Journal Year: 2024, Volume and Issue: 5(4)

Published: Jan. 1, 2024

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact endurance exercise training on molecular signaling within across tissues remains to be delineated. The Molecular Transducers Physical Activity Consortium (MoTrPAC) was established characterize networks underlying adaptive response exercise. Here, we describe studies undertaken by Preclinical Animal Sites Studies component MoTrPAC, in which sought develop implement standardized protocol large cohort rats. To this end, Adult (6-mo) Aged (18-mo) female (n = 151) male 143) Fischer 344 rats were subjected progressive treadmill (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary studied as control group. A total 18 solid tissues, well blood, plasma, feces, collected establish publicly accessible biorepository extensive omics-based analyses MoTrPAC. Treadmill highly effective, with robust improvements skeletal muscle citrate synthase little 1-2 wk maximum run speed maximal oxygen uptake 4-8 wk. For body mass composition, notable age- sex-dependent responses observed. This work mature, treadmill-trained represents most comprehensive tissue biorepository, date, provides an unprecedented resource studying temporal-, sex-, age-specific preclinical rat model.

Language: Английский

Citations

9
The impact of exercise on gene regulation in association with complex trait genetics DOI Creative Commons
Nikolai G. Vetr, Nicole R. Gay, Stephen B. Montgomery

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 1, 2024

Endurance exercise training is known to reduce risk for a range of complex diseases. However, the molecular basis this effect has been challenging study and largely restricted analyses either few or easily biopsied tissues. Extensive transcriptome data collected across 15 tissues during in rats as part Molecular Transducers Physical Activity Consortium provided unique opportunity clarify how can affect tissue-specific gene expression further suggest adaptation may impact disease-associated genes. To build map, we integrate multi-tissue atlas changes with gene-disease targets, genetic regulation expression, trait relationship humans. Consensus from multiple approaches prioritizes specific genes where endurance impacts disease-relevant expression. Specifically, identify total 5523 trait-tissue-gene triplets serve valuable starting point future investigations [Exercise; Transcription; Human Phenotypic Variation].

Language: Английский

Citations

9
The role of skeletal muscle respiratory capacity in exercise performance DOI Creative Commons
Pablo M. García-Rovés,

Jorge Alvarez-Luis,

Sandra Cutanda-Tesouro

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise DOI Open Access
Taylor J. Kelty, Nathan R. Kerr, Chien-Chih Chou

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of on brain health during exercise, healthy 6‐month‐old female rats underwent viral knockdown rate‐limiting enzyme liver that catalyses first reaction ketogenesis: 3‐hydroxymethylglutaryl‐CoA synthase 2 (HMGCS2). Rats were then subjected either a bout acute or 4 weeks chronic treadmill running (5 days/week) and cognitive behavioural testing. Acute elevated plasma concentration 1 h following exercise. Hepatic HMGCS2 knockdown, verified protein expression, reduced after 48 Proteomic analysis enrichment frontal cortex revealed markers mitochondrial function significantly state 3 complex I + II respiration isolated mitochondria from Spatial memory synaptic plasticity knockdown. These deficiencies prevented training. In summary, data propose ketogenesis is required maintain cognition function, irrespective training status, can overcome neuropathology caused insufficient ketogenesis. results establish mechanistic link between enhance our understanding how peripheral tissue metabolism influences health. image Key points Decades literature demonstrate This study provides set suggest cognition, function. indicate protect against decline compromised prompting further investigation

Language: Английский

Citations

1
Metabolic interplays between the tumour and the host shape the tumour macroenvironment DOI
Patricia Altea‐Manzano, Amanda R. Decker-Farrell, Tobias Janowitz

et al.

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

Citations

1
Relevance of proteomics and metabolomics approaches to overview the tumorigenesis and better management of cancer DOI
Pooja Singh, Yashika Walia, Shagun Gupta

et al.

3 Biotech, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 11, 2025

Language: Английский

Citations

1
Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training DOI Creative Commons
Mark Viggars,

Hannah E Berko,

Stuart J. Hesketh

et al.

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 86, P. 101980 - 101980

Published: June 29, 2024

In this investigation, we addressed the contribution of core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses exercise and remodeling response training. Additionally, adopted a systems biology approach investigate how loss BMAL1 altered peripheral tissue homeostasis as well training adaptations iWAT, liver, heart, lung male mice.

Language: Английский

Citations

7