Cited by 301Adipose Tissue and MetabolismMuscle Physiology and DisordersAdipokines, Inflammation, and Metabolic Diseases

Myostatin Knockout Drives Browning of White Adipose Tissue through Activating the AMPK-PGC1α-Fndc5 Pathway in Muscle

Open access
Shan, Tizhong, Liang, Xinrong, Bi, Pengpeng, Kuang, Shihuan·2013·The FASEB Journal

Abstract

Myostatin (Mstn) is predominantly expressed in skeletal muscles and plays important roles in regulating muscle growth and development, as well as fat deposition. Mstn-knockout (Mstn(-/-)) mice exhibit increased muscle mass due to both hypertrophy and hyperplasia, and leaner body composition due to reduced fat mass. Here, we show that white adipose tissue (WAT) of Mstn(-/-) develops characteristics of brown adipose tissue (BAT) with dramatically increased expression of BAT signature genes, including Ucp1 and Pgc1α, and beige adipocyte markers Tmem26 and CD137. Strikingly, the observed browning phenotype is non-cell autonomous and is instead driven by the newly defined myokine irisin (Fndc5) secreted from Mstn(-/-) skeletal muscle. Within the muscle, Mstn(-/-) leads to increased expression of AMPK and its phosphorylation, which subsequently activates PGC1α and Fndc5. Together, our study defines a paradigm of muscle-fat crosstalk mediated by Fndc5, which is up-regulated and secreted from muscle to induce beige cell markers and the browning of WAT in Mstn(-/-) mice. These results suggest that targeting muscle Mstn and its downstream signaling represents a therapeutic approach to treat obesity and type 2 diabetes.

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Crossref · 10.1096/fj.12-225755

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Authors
Shan, T., Liang, X., Bi, P., & Kuang, S.
Affiliations
Purdue University West Lafayette (US)
Venue
The FASEB Journal
Publisher
Wiley
Published
2013-01-29
Volume
27
Issue
5
Pages
1981-1989
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2124205424
Cited by
301
References
49
Citations by year
2026: 6 · 2025: 15 · 2024: 15 · 2023: 16 · 2022: 30 · 2021: 28 · 2020: 20 · 2019: 26 · 2018: 19 · 2017: 26 · 2016: 21 · 2015: 30 · 2014: 31 · 2013: 18
FWCI
23.21
Type
journal article
Language
en
Open access
Locations
  • The FASEB Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Muscular Dystrophy Association
  • National Institutes of Health
  • U.S. Department of Agriculture
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
myostatin, white adipose tissue browning, brown adipose tissue, AMPK, PGC-1α, FNDC5, irisin, beige adipocytes, skeletal muscle, non-cell-autonomous signaling, obesity, type 2 diabetes, UCP1, 4-1BB
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adenylate Kinase, Animals, Adipose Tissue, Brown, Fibronectins, Transcription Factors, Trans-Activators, Up-Regulation, Mice, Knockout, Muscle, Skeletal, Mice, Adipose Tissue, White, Myostatin

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