MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16
Open accessAbstract
Brown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3'UTR of Prdm16. Antagonism of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels are downregulated in mice exposed to cold, resulting in de novo generation of satellite cell-derived brown adipocytes. Therefore, microRNA-133 represents an important therapeutic target for the treatment of obesity.
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S100B stimulates NF-κB activity with resultant upregulation of YY1 and YY1-dependent inhibition of microRNA-133, ultimately leading to the transition of myoblasts into adipocytes.
“In turn, S100B stimulates NF‐κB activity with resultant upregulation of YY1 and YY1‐dependent inhibition of microRNA‐133, a promyogenic and anti‐adipogenic microRNA,[ 32 ] ultimately leading to the transition of myoblasts into adipocytes.[ 31 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [32]
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- Authors
- Yin, H., Pasut, A., Soleimani, V. D., Bentzinger, C. F., Antoun, G., Thorn, S., Seale, P., Fernando, P., van IJcken, W., Grosveld, F., Dekemp, R. A., Boushel, R., Harper, M.-E., & Rudnicki, M. A.
- Affiliations
- Ottawa Hospital Research Institute (CA)
- University of Ottawa (CA)
- Ottawa Heart Institute (CA)
- University of Pennsylvania (US)
- Nordion (Canada) (CA)
- Erasmus MC (NL)
- University of Copenhagen (DK)
- Corresponding author
- Rudnicki, Michael A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 17
- Issue
- 2
- Pages
- 210-224
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3641657
- OpenAlex
- W2004803010
- Cited by
- 293
- References
- 42
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 19 · 2023: 18 · 2022: 12 · 2021: 18 · 2020: 33 · 2019: 20 · 2018: 24 · 2017: 25 · 2016: 15 · 2015: 31 · 2014: 37 · 2013: 25
- FWCI
- 25.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044031)
- Ontario Research Foundation (MOP81288)
- Canadian Institutes of Health Research
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- microRNA-133, PRDM16, brown adipose tissue, skeletal muscle satellite cells, brown adipocyte differentiation, thermogenesis, muscle regeneration, energy expenditure, glucose tolerance, diet-induced obesity, cold exposure, myogenic lineage, 3' UTR targeting
- MeSH terms
- Animals, Base Sequence, Adipose Tissue, Brown, Cell Differentiation, Cold Temperature, DNA-Binding Proteins, Energy Metabolism, Glucose Tolerance Test, Molecular Sequence Data, Regeneration, Transcription Factors, Down-Regulation, Cell Lineage, 3' Untranslated Regions, Satellite Cells, Skeletal Muscle, MicroRNAs, Multipotent Stem Cells, Mice, Adipocytes, Brown
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