Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109221 - 109221

Published: Feb. 15, 2024

Fat infiltration in skeletal muscle (also known as myosteatosis) is now recognized a distinct disease from sarcopenia and directly related to declining capacity. Hence, understanding the origins regulatory mechanisms of fat vital for maintaining development improving human health. In this article, we summarized triggering factors such aging, metabolic diseases syndromes, nonmetabolic diseases, injury that all induce muscle. We discussed recent advances on cellular found several cell types including myogenic cells non-myogenic contribute myosteatosis. Furthermore, reviewed molecular mechanism, detection methods, intervention strategies Based current findings, our review will provide new insight into regulating function lipid metabolism treating muscle-related diseases.

Language: Английский

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Exploring the therapeutic potential of fibroadipogenic progenitors in muscle disease

Journal of Neuromuscular Diseases, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 1, 2025

Skeletal muscle relies on its inherent self-repair ability to withstand continuous mechanical damage. Myofiber-intrinsic processes facilitate the repair of damage sarcolemma and sarcomeres, but it is coordinated interaction between muscle-resident satellite stromal cells that are crucial in regeneration muscles replace lost fibers. Fibroadipogenic progenitors (FAPs), mesenchymal notable for their role creating dynamic niche required support long-term homeostasis regeneration. While FAP-mediated extracellular matrix formation establishment a homeostatic essential maintaining health, excessive accumulation FAPs aberrant differentiation leads fibrofatty degeneration hallmark myopathies muscular dystrophies. Recent advancements, including single-cell RNA sequencing vivo analysis FAPs, providing deeper insights into functions specialization shedding light roles both health disease. This review will explore above insights, discussing how FAP dysregulation contributes diseases. It offer concise overview potential therapeutic interventions targeting restore disrupted interactions among cells, ultimately addressing degenerative loss neuromuscular

Language: Английский

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Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 97, P. 101277 - 101277

Published: May 24, 2024

Excessive accumulation of intermuscular adipose tissue (IMAT) is a common pathological feature in various metabolic and health conditions can cause muscle atrophy, reduced function, inflammation, insulin resistance, cardiovascular issues, unhealthy aging. Although IMAT results from fat muscle, the mechanisms underlying its onset, development, cellular components, functions remain unclear. levels are influenced by several factors, such as changes environment, type origin, extent duration trauma, persistent activation fibro-adipogenic progenitors (FAPs). FAPs diverse transcriptionally heterogeneous population stromal cells essential for maintenance, neuromuscular stability, regeneration. However, cases chronic inflammation conditions, expand differentiate into adipocytes, resulting development abnormal ectopic IMAT. This review discusses role adipogenesis how they remodel It highlights evidence supporting FAP-derived adipocytes constituents IMAT, emphasizing their significance maintenance well involvement disorders, pathologies diseases. We also investigated intricate molecular pathways cell interactions governing FAP behavior, adipogenesis, diseases deconditioning. Finally, we hypothesize that impaired flexibility dysfunctional muscles impacts FAPs, leading to A deeper understanding biology regulating behavior fate new therapeutic strategies debilitating conditions.

Language: Английский

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Migrasomes from adipose derived stem cells enrich CXCL12 to recruit stem cells via CXCR4/RhoA for a positive feedback loop mediating soft tissue regeneration

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 3, 2024

Abstract Background Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved recruitment of ASCs post injury was mediated by chemokine CXCL12, but mechanism which CXCL12 is generated after remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated Methods Discrepant asymmetrical regeneration mice model were established, HE staining, immunofluorescent western blot qPCR conducted confirm role Characterization ASC-derived carried out confocal microscopy, scanning electron transmission microscopy as well analysis. The function further testified assisting with isolated vivo vitro transwell combined co-culture system. Results Here, show first time generate enriched mediate from promote migration activating CXCR4/RhoA signaling vitro. Chemoattracted facilitate regeneration, demonstrated upregulation an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment Thus, new therapeutic target Conclusions Our findings reveal previously unknown mediating generating migrasomes. can restore recruiting cells, highlighting potential application regenerative medicine.

Language: Английский

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The reciprocity of skeletal muscle and bone: an evolving view from mechanical coupling, secretory crosstalk to stem cell exchange

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: March 4, 2024

Introduction: Muscle and bone constitute the two main parts of musculoskeletal system generate an intricately coordinated motion system. The crosstalk between muscle has been under investigation, leading to revolutionary perspectives in recent years. Method results: In this review, evolving concept muscle-bone interaction from mechanical coupling, secretory stem cell exchange was explained sequence. theory coupling stems observation that development maintenance mass are largely dependent on muscle-derived loads, which later proved by Wolff’s law, Utah paradigm Mechanostat hypothesis. Then gradually recognized as endocrine organs, can secrete various cytokines modulate tissue homeostasis remodeling each other. latest view presented a more direct way: resident mesenchymal stromal skeletal muscle, i.e., fibro-adipogenic progenitors (FAPs), could migrate injury site contribute regeneration. Emerging evidence even reveals ectopic source FAPs outside system, highlighting its dynamic property. Conclusion: have established critical connecting bone, provides new modality study inter-tissue communication. A comprehensive integrated perspective will facilitate in-depth research promote novel therapeutic avenues treating disorders.

Language: Английский

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Single‐cell RNA‐seq reveals novel interaction between muscle satellite cells and fibro‐adipogenic progenitors mediated with FGF7 signalling

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(4), P. 1388 - 1403

Published: May 16, 2024

Abstract Background Muscle satellite cells (MuSCs) exert essential roles in skeletal muscle adaptation to growth, injury and ageing, their functions are extensively modulated by microenvironmental factors. However, the current knowledge about interaction of MuSCs with niche is quite limited. Methods A 10× single‐cell RNA sequencing (scRNA‐seq) was performed on porcine longissimus dorsi soleus (SOL) muscles generate a transcriptomic dataset myogenic other cell types. Sophisticated bioinformatic analyses, including unsupervised clustering analysis, marker gene, gene set variation analysis (GSVA), AUCell, pseudotime velocity were explore heterogeneity cells. CellChat used demonstrate cell–cell communications across subpopulations cells, especially fibro‐adipogenic progenitors (FAPs). Integrated human mice datasets verify expression FGF7 diverse species. The role MuSC proliferation evaluated through administering recombinant MuSCs, C2C12, cardiotoxin (CTX)‐injured d ‐galactose ( ‐gal)‐induced ageing model. Results ScRNA‐seq totally figured out five types myo‐lineage FAPs, further classified into six subpopulations, termed as RCN3 + , S100A4 ID3 cycling (MKI67 ), MYF6 MYMK respectively. There higher proportion c ycling SOL population. uncovered particular impact FAPs mediated FGF7, which relatively highly expressed samples. Administration (10 ng/mL) significantly increased EdU C2C12 4.03 ± 0.81% P < 0.01) 6.87 2.17% 0.05), respectively, knockdown FGFR2 dramatically abolished pro‐proliferating effects 0.05). In CTX‐injured muscle, ratio /Pax7 15.68 5.45% 0.05) elevated number eMyHC regenerating myofibres 19.7 4.25% 0.01). Under ‐gal stimuli, reduced γH2AX 17.19 3.05% induced 4.34 1.54% restored myofibre size loss running exhaustion vivo (all Conclusions Our scRNA‐seq reveals novel between FGF7–FGFR2. Exogenous augments thus benefits regeneration counteracts age‐related myopathy.

Language: Английский

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Cytokines and exosomal miRNAs in skeletal muscle–adipose crosstalk

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(10), P. 666 - 681

Published: Aug. 18, 2023

Language: Английский

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Extracellular matrix: the critical contributor to skeletal muscle regeneration—a comprehensive review

Inflammation and Regeneration, Journal Year: 2023, Volume and Issue: 43(1)

Published: Nov. 27, 2023

Abstract The regenerative ability of skeletal muscle (SM) in response to damage, injury, or disease is a highly intricate process that involves the coordinated activities multiple cell types and biomolecular factors. Of these, extracellular matrix (ECM) considered fundamental component SM ability. This review briefly discusses myogenesis regeneration, roles played by satellite cells (MSCs), other cells, ECM components, effects their dysregulations on these processes. In addition, we various scaffolds biomaterials used for applications, recent advances scaffold research, impacts tissue engineering especially context severe which frequently results substantial loss impaired capacity. was undertaken provide comprehensive overview stem significance enhance understanding essential role during regeneration.

Language: Английский

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MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 30, 2024

Abstract Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli injuries, range stem/progenitor cells, with stem cells or satellite (MuSCs) being the predominant cell type, are rapidly activated repair regenerate skeletal within weeks. Under normal conditions, MuSCs remain quiescent state, but become proliferative differentiate into new injury. addition MuSCs, some interstitial progenitor (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, expressing PW1 negative for Pax7 (PICs), side population (SPCs), CD133-positive Twist2-positive have been identified playing direct indirect roles regenerating tissue. Here, we highlight heterogeneity, molecular markers, functional properties these explore role homeostasis, aging, muscle-related diseases. This review provides critical insights future therapies aimed at treating

Language: Английский

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The myokine CCL5 recruits subcutaneous preadipocytes and promotes intramuscular fat deposition in obese mice

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(5), P. C1320 - C1333

Published: March 18, 2024

Intramuscular fat (IMF) refers to the lipid stored in skeletal muscle tissue. The number and size of intramuscular adipocytes are primary factors that regulate IMF content. can be derived from either situ or ectopic migration. In this study, it was discovered regulation levels is achieved through chemokine (C-C motif) ligand 5 (CCL5)/chemokine receptor (CCR5) pathway by modulating adipocyte coculture experiments, C2C12 myotubes were more effective promoting migration 3T3-L1 preadipocytes than myoblasts, along with increasing CCL5. Correspondingly, overexpressing CCR5, one receptors CCL5, facilitated their Conversely, application CCL5/CCR5 inhibitor, MARAVIROC (MVC), reduced vivo, transplanted experiments subcutaneous adipose tissue (SCAT) transgenic mice expressing green fluorescent protein (GFP) provided evidence injecting recombinant CCL5 (rCCL5) into promotes muscle. level increased obesity. Blocking axis MVC inhibited deposition, whereas elevated promoted deposition obese mice. These results establish a link between pathway, which could have potential for

Language: Английский

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