Downstream Signaling Pathways in Mouse Adipose Tissues Following Acute In Vivo Administration of Fibroblast Growth Factor 21
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FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation.
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More recent studies failed to observe increases in plasma adiponectin levels in response to acute FGF21 administration.
“However, more recent studies have challenged these findings by failing to observe increases in plasma adiponectin levels in response to acute FGF21 administration (11, 95).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [95]
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Localization of FGF21 Protein and Lipid Metabolism-Related Genes in Camels
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Therapeutic potential of FGF21 in diabetes
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A comparison of data visualization tools: A case study in health-related research
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- Authors
- Muise, E. S., Souza, S., Chi, A., Tan, Y., Zhao, X., Liu, F., Dallas-yang, Q., Wu, M., Sarr, T., Zhu, L., Guo, H., Li, Z., Li, W., Hu, W., Jiang, G., Paweletz, C. P., Hendrickson, R. C., Thompson, J. R., Mu, J., Berger, J. P., & Mehmet, H.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Muise, Eric S.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-06
- Volume
- 8
- Issue
- 9
- Pages
- e73011
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3765203
- OpenAlex
- W1993551202
- Cited by
- 57
- References
- 37
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 10 · 2016: 5 · 2015: 9 · 2014: 5 · 2013: 2
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- FGF21, adipose tissue, adipocytes, signal transduction, target engagement biomarkers, phosphoproteomics, gene expression profiling, white adipose tissue, db/db mice, high-fat diet, insulin receptor signaling, ERK signaling, lipid metabolism, glucose uptake, obesity, diabetes mellitus, obesity treatment
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Body Weight, Adipose Tissue, Brown, Fibroblast Growth Factors, Gene Expression Regulation, Insulin, Male, Phosphoproteins, Transcription, Genetic, Reproducibility of Results, Signal Transduction, Cluster Analysis, Adipocytes, Proteome, Gene Expression Profiling, 3T3-L1 Cells, Mice, Adipose Tissue, White
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