Dataset Information

Role of Metabolic Stress and Exercise in Regulating Fibro/Adipogenic Progenitors.

ABSTRACT: Obesity is a major public health concern and is associated with decreased muscle quality (i.e., strength, metabolism). Muscle from obese adults is characterized by increases in fatty, fibrotic tissue that decreases the force producing capacity of muscle and impairs glucose disposal. Fibro/adipogenic progenitors (FAPs) are muscle resident, multipotent stromal cells that are responsible for muscle fibro/fatty tissue accumulation. Additionally, they are indirectly involved in muscle adaptation through their promotion of myogenic (muscle-forming) satellite cell proliferation and differentiation. In conditions similar to obesity that are characterized by chronic muscle degeneration, FAP dysfunction has been shown to be responsible for increased fibro/fatty tissue accumulation in skeletal muscle, and impaired satellite cell function. The role of metabolic stress in regulating FAP differentiation and paracrine function in skeletal muscle is just beginning to be unraveled. Thus, the present review aims to summarize the recent literature on the role of metabolic stress in regulating FAP differentiation and paracrine function in skeletal muscle, and the mechanisms responsible for these effects. Furthermore, we will review the role of physical activity in reversing or ameliorating the detrimental effects of obesity on FAP function.

SUBMITTER: Collao N

PROVIDER: S-EPMC6997132 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Role of Metabolic Stress and Exercise in Regulating Fibro/Adipogenic Progenitors.

Collao Nicolas N Farup Jean J De Lisio Michael M

Frontiers in cell and developmental biology 20200128

Obesity is a major public health concern and is associated with decreased muscle quality (i.e., strength, metabolism). Muscle from obese adults is characterized by increases in fatty, fibrotic tissue that decreases the force producing capacity of muscle and impairs glucose disposal. Fibro/adipogenic progenitors (FAPs) are muscle resident, multipotent stromal cells that are responsible for muscle fibro/fatty tissue accumulation. Additionally, they are indirectly involved in muscle adaptation thro ...[more]

PMID: 32047748

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Project description:Muscle resident fibro-adipogenic progenitors (FAPs), support muscle regeneration by releasing cytokines that stimulate the differentiation of myogenic stem cells. However, in non-physiological contexts (myopathies, atrophy, aging) FAPs cause fibrotic and fat infiltrations that impair muscle function. We set out to perform a fluorescence microscopy-based screening to identify compounds that perturb the differentiation trajectories of these multipotent stem cells. From a primary screen of 1,120 FDA/EMA approved drugs, we identified 34 compounds as potential inhibitors of adipogenic differentiation of FAPs isolated from the murine model (mdx) of Duchenne muscular dystrophy (DMD). The hit list from this screen was surprisingly enriched with compounds from the glucocorticoid (GCs) chemical class, drugs that are known to promote adipogenesis in vitro and in vivo. To shed light on these data, three GCs identified in our screening efforts were characterized by different approaches. We found that like dexamethasone, budesonide inhibits adipogenesis induced by insulin in sub-confluent FAPs. However, both drugs have a pro-adipogenic impact when the adipogenic mix contains factors that increase the concentration of cAMP. Gene expression analysis demonstrated that treatment with glucocorticoids induces the transcription of Gilz/Tsc22d3, an inhibitor of the adipogenic master regulator PPAR?, only in anti-adipogenic conditions. Additionally, alongside their anti-adipogenic effect, GCs are shown to promote terminal differentiation of satellite cells. Both the anti-adipogenic and pro-myogenic effects are mediated by the glucocorticoid receptor and are not observed in the presence of receptor inhibitors. Steroid administration currently represents the standard treatment for DMD patients, the rationale being based on their anti-inflammatory effects. The findings presented here offer new insights on additional glucocorticoid effects on muscle stem cells that may affect muscle homeostasis and physiology.

Dataset Information

Role of Metabolic Stress and Exercise in Regulating Fibro/Adipogenic Progenitors.

Publications

Role of Metabolic Stress and Exercise in Regulating Fibro/Adipogenic Progenitors.

Similar Datasets

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