Severe Muscle Deconditioning Triggers Early Extracellular Matrix Remodeling and Resident Stem Cell Differentiation into Adipocytes in Healthy Men

Abstract

Besides the loss of muscle mass and strength, increased intermuscular adipose tissue (IMAT) is now a well-recognized consequence of muscle deconditioning as experienced in prolonged microgravity. IMAT content may alter the muscle stem cell microenvironment. We hypothesized that extracellular matrix structure alterations and microenvironment remodeling induced by fast and severe muscle disuse could modulate fibro-adipogenic progenitor fate and behavior. We used the dry immersion (DI) model that rapidly leads to severe muscle deconditioning due to drastic hypoactivity. We randomly assigned healthy volunteers (n = 18 men) to the control group (only DI, n = 9; age = 33.8 ± 4) or to the DI + thigh cuff group (n = 9; age = 33.4 ± 7). Participants remained immersed in the supine position in a thermo-neutral water bath for 5 days. We collected vastus lateralis biopsies before (baseline) and after DI. 5 days of DI are sufficient to reduce muscle mass significantly, as indicated by the decreased myofiber cross-sectional area in vastus lateralis samples (−18% vs. baseline, p < 0.05). Early and late adipogenic differentiation transcription factors protein levels were upregulated. Platelet-derived growth Factors alpha (PDGFR⍺) protein level and PDGFR⍺-positive cells were increased after 5 days of DI. Extracellular matrix structure was prone to remodeling with an altered ECM composition with 4 major collagens, fibronectin, and Connective Tissue Growth Factor mRNA decreases (p < 0.001 vs. baseline). Wearing thigh cuffs did not have any preventive effect on the measured variable. Our results show that altered extracellular matrix structure and signaling pathways occur early during DI, a severe muscle wasting model, favoring fibro-adipogenic progenitor differentiation into adipocytes.

A single chemotherapy administration induces muscle atrophy, mitochondrial alterations and apoptosis in breast cancer patients

“…If skeletal muscle atrophy was classically reported at the end of the chemotherapy treatment 3,4,14 or after a single administration of chemotherapy in preclinical models, 6 we demonstrated, in patients, that a single dose of EC drastically reduced muscle fibres CSA. Such a decrease in muscle fibres CSA in humans highlights an extreme skeletal muscle deconditioning condition given that a similar decrease (≈À20%) have been reported after 5 days of dry immersion, 16 a ground-based model aiming to mimic the effects of microgravity. In addition, the decrease found in our patients (À25%) is comparable with the considerable effect of 60 years of healthy aging, 17 emphasizing the potent effect of EC on skeletal muscle in only 4 days.…”

The State of the Organs of the Female Reproductive System after a 5-Day “Dry” Immersion

“…Another generally accepted ground-based model is “dry” immersion [ 12 , 13 , 14 ]. However, similar to the bed-rest model, studies during “dry” immersion are most often aimed at the musculoskeletal, nervous, and cardiovascular systems [ 15 , 16 , 17 , 18 ]. Moreover, the first “dry” immersion study with women as the subjects that lasted 3 days was conducted in 2020 [ 19 ].…”

Expression of intramuscular extracellular matrix proteins in vastus lateralis muscle fibres between atrophic and non-atrophic COPD

“…The differences in ECM composition between atrophic and non-atrophic COPD were limited to a decrease in mRNA expression of COL1A1 , FN1 , TNC and BGN in atrophic COPD. This suggests that atrophic COPD muscle has lower baseline transcriptional activity, which could be due to severe muscle deconditioning [ 10 , 25 ]. While atrophic muscle presented decreased contractile muscle tissue, the differences in ECM mRNA expression between atrophic and not atrophic COPD were not translated at the protein level, potentially indicating an accumulation of long-lived ECM proteins and dysregulated proteostasis, as is typically observed during deconditioning and ageing [ 10 , 25 ].…”

“…The aim of this retrospective analysis was to investigate the expression of selected intramuscular ECM proteins that are considered to be crucial for muscle homeostasis [ 5 , 9 ] in the vastus lateralis muscle of COPD patients. Considering that altered intramuscular ECM composition has been found in a number of pathological states and long-term conditions manifesting muscle wasting [ 6 , 7 , 10 ], it was anticipated that ECM expression would differ in the vastus lateralis muscle of COPD patients with muscle wasting (atrophic COPD) compared to those without muscle wasting (non-atrophic COPD).…”