IL-1β- and IL-4-polarized macrophages have opposite effects on adipogenesis of intramuscular fibro-adipogenic progenitors in humans
Open accessAbstract
Intramuscular fat deposition represents a negative prognostic factor for several myopathies, metabolic diseases and aging. Fibro-adipogenic progenitors (FAPs) are considered as the main source of intramuscular adipocytes, but the mechanisms controlling their adipogenic potential are still not elucidated in humans. The aim of this study was to explore the regulation of human FAP adipogenesis by macrophages. We found that CD140a-expressing FAPs were located close to CD68 positive macrophages in muscles from patients with Duchenne muscular dystrophy (DMD). This strongly suggests a potential interaction between FAPs and macrophages in vivo. Isolated human primary FAPs were then differentiated in the presence of conditioned media obtained from primary blood monocyte-polarized macrophages. Molecules released by IL-1β-polarized macrophages (M(IL-1β)) drastically reduced FAP adipogenic potential as assessed by decreased cellular lipid accumulation and reduced gene expression of adipogenic markers. This was associated with an increased gene expression of pro-inflammatory cytokines in FAPs. Conversely, factors secreted by IL-4-polarized macrophages (M(IL-4)) enhanced FAP adipogenesis. Finally, the inhibition of FAP adipocyte differentiation by M(IL-1β) macrophages requires the stimulation of Smad2 phosphorylation of FAPs. Our findings identify a novel potential crosstalk between FAPs and M(IL-1β) and M(IL-4) macrophages in the development of adipocyte accumulation in human skeletal muscles.
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M1 macrophages reduce, while M2 macrophages enhance, FAP adipogenic potential.
“Through their secretome, M1 macrophages reduce, while M2 macrophages enhance, FAP adipogenic potential”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Moratal et al., 2018
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References 62 · Cited by 101
- Authors
- Moratal, C., Raffort, J., Arrighi, N., Rekima, S., Schaub, S., Dechesne, C. A., Chinetti, G., & Dani, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Corresponding author
- Dani, C.
- Venue
- Scientific Reports
- Published
- 2018-11-19
- Volume
- 8
- Issue
- 1
- Pages
- 17005-17005
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6242986
- OpenAlex
- W2901294232
- Cited by
- 101
- References
- 62
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 9 · 2023: 12 · 2022: 10 · 2021: 22 · 2020: 12 · 2019: 5
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-16-CE14-0001)
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Duchenne Parent Project
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- intramuscular adipogenesis, fibro-adipogenic progenitors, macrophage polarization, IL-1β, IL-4, Duchenne muscular dystrophy, intramuscular fat deposition, Smad2 phosphorylation, inflammatory cytokines, skeletal muscle, CD68
- MeSH terms
- Adolescent, Adult, Cell Differentiation, Cells, Cultured, Child, Child, Preschool, Female, Humans, Infant, Macrophages, Male, Regeneration, Stem Cells, Interleukin-4, Case-Control Studies, Adipocytes, Muscle, Skeletal, Muscular Dystrophy, Duchenne, Adipogenesis, Interleukin-1beta, Young Adult
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