Follistatin targets distinct pathways to promote Brown adipocyte characteristics in Brown and white adipose tissues
Open accessAbstract
We previously demonstrated that Fst expression is highest in brown adipose tissue (BAT) and skeletal muscle, but is also present at substantial levels in epididymal and subcutaneous white adipose tissues (WATs). Fst promotes mouse brown preadipocyte differentiation and promotes browning during differentiation of mouse embryonic fibroblasts. Fst-transgenic (Fst-Tg) mice show substantial increases in circulating Fst levels and increased brown adipose mass. BAT of Fst-Tg mice had increased expression of brown adipose-associated markers including uncoupling protein 1 (UCP1), PRDM16, PGC-1α, and Glut4. WATs from Fst-Tg mice show upregulation of brown/beige adipose markers and significantly increased levels of phosphorylated p38 MAPK/ERK1/2 proteins compared with the wild-type (WT) mice. Pharmacological inhibition of pp38 MAPK/pERK1/2 pathway of recombinant mouse Fst (rFst) treated differentiating 3T3-L1 cells led to significant blockade of Fst-induced UCP1 protein expression. On the other hand, BAT from Fst-Tg mice or differentiating mouse BAT cells treated with rFst show dramatic increase in Myf5 protein levels as well as upregulation of Zic1 and Lhx8 gene expression. Myf5 levels were significantly downregulated in Fst knock-out embryos and small inhibitory RNA-mediated inhibition of Myf5 led to significant inhibition of UCP1, Lhx8, and Zic1 gene expression and significant blockade of Fst-induced induction of UCP1 protein expression in mouse BAT cells. Both interscapular BAT and WAT tissues from Fst-Tg mice display enhanced response to CL316,243 treatment and decreased expression of pSmad3 compared with the WT mice. Therefore, our results indicate that Fst promotes brown adipocyte characteristics in both WAT and BAT depots in vivo through distinct mechanisms.
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FST increases phosphorylation of MAPK/ERK1/2 proteins in WAT and increases expression of Myf5 protein in BAT, which increases UCP1 expression in both tissues.
“FST functions to increase the phosphorylation of MAPK/ERK1/2 proteins in WAT and increase the expression of Myf5 protein in BAT, which increases UCP1 expression in both tissues [198].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [198]
Mice overexpressing FST have increased expression of thermogenic markers, including UCP1, in WAT and BAT.
“A recent study demonstrated that mice overexpressing FST have increased expression of thermogenic markers, including UCP1, in WAT and BAT [198].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [198]
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Hepatokines and metabolism: Deciphering communication from the liver
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Self-citation
- Authors
- Singh, R., Braga, M., Reddy, S. T., Lee, S.-J., Parveen, M., Grijalva, V., Vergnes, L., & Pervin, S.
- Affiliations
- Charles R. Drew University of Medicine and Science (US)
- Obstetrics and Gynecology and
- Johns Hopkins University (US)
- Medicine, Molecular and Medical Pharmacology and
- University of California, Los Angeles (US)
- Corresponding author
- Singh, Rajan
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2017-01-16
- Volume
- 158
- Issue
- 5
- Pages
- 1217-1230
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC5460830
- OpenAlex
- W2604294205
- Cited by
- 54
- References
- 46
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 11 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 2
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (SC1AG049682)
- National Cancer Institute (SC1CA165865)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060636)
- National Institute on Minority Health and Health Disparities (S21MD000103, U54MD007598)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- follistatin, brown adipose tissue, white adipose tissue, brown adipocyte differentiation, UCP1, Myf5, Lhx8, ZIC1, Smad3, CL316,243, PRDM16, PGC-1α
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Signal Transduction, Thermogenesis, Follistatin, 3T3-L1 Cells, Mice, Adipose Tissue, White, Adipocytes, Brown, Adipocytes, White, Cell Transdifferentiation
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