Whole transcriptome analysis and validation of metabolic pathways in subcutaneous adipose tissues during FGF21-induced weight loss in non-human primates
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Fibroblast growth factor 21 (FGF21) induces weight loss in mouse, monkey, and human studies. In mice, FGF21 is thought to cause weight loss by stimulating thermogenesis, but whether FGF21 increases energy expenditure (EE) in primates is unclear. Here, we explore the transcriptional response and gene networks active in adipose tissue of rhesus macaques following FGF21-induced weight loss. Genes related to thermogenesis responded inconsistently to FGF21 treatment and weight loss. However, expression of gene modules involved in triglyceride (TG) synthesis and adipogenesis decreased, and this was associated with greater weight loss. Conversely, expression of innate immune cell markers was increased post-treatment and was associated with greater weight loss. A lipogenesis gene module associated with weight loss was evaluated by testing the function of member genes in mice. Overexpression of NRG4 reduced weight gain in diet-induced obese mice, while overexpression of ANGPTL8 resulted in elevated TG levels in lean mice. These observations provide evidence for a shifting balance of lipid storage and metabolism due to FGF21-induced weight loss in the non-human primate model, and do not fully recapitulate increased EE seen in rodent and in vitro studies. These discrepancies may reflect inter-species differences or complex interplay of FGF21 activity and counter-regulatory mechanisms.
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In DIO non-human primates, FGF21 or FGF21-analog administration promotes weight loss.
“In DIO non-human primates, similarly to rodents, FGF21 or FGF21-analog administration also promotes weight loss40,81,86.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [86]
Some studies report FGF21-mediated weight loss without effects on food intake; another study using PF-05231023 reports weight loss attributable to significant decreases in food intake.
“whereas some studies have reported FGF21-mediated weight loss without effects on food intake40,86, another study using an FGF21 analogue (PF-05231023) in non-human primates has reported that the weight loss is attributable to significant decreases in food intake81.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [86]
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Self-citationMaung, J. N., Chen, Y., Hoose, K. S., Adler, R. E., Hariri, H., Dickson, M. J., Hetrick, T. A., Ferguson, G. A., Schill, R. L., Mori, H., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.194882 · Cited by 1 · see citing works
Бажан, Н. М., & En, M. (2023) · Успехи физиологических наук · doi:10.31857/s0301179823040033
Fujita, Y., Ishibuchi, T., Uematsu, A., Hayashi, T., & Obata, F. (2025) · Scientific Reports · doi:10.1038/s41598-025-16749-0
- Authors
- Murray, S. A., Dalbøge, L. S., Baquero, K., Sanford, C. A., Misquith, A., Mercer, A. J., Meek, T. H., Guldbrandt, M., Andersen, B., Kievit, P., Grove, K. L., & Kutlu, B.
- Affiliations
- Novo Nordisk (United States) (US)
- Gubra (Denmark) (DK)
- Novo Nordisk (Denmark) (DK)
- Oregon National Primate Research Center (US)
- Corresponding author
- Murray, Sara A.
- Kutlu, Burak
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-04-29
- Volume
- 10
- Issue
- 1
- Pages
- 7287-7287
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7190698
- OpenAlex
- W3022111741
- Cited by
- 12
- References
- 73
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 2
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- FGF21, weight loss, subcutaneous adipose tissue, rhesus monkeys, energy expenditure, thermogenesis, triglyceride synthesis, adipogenesis, lipogenesis, innate immune cells, ANGPTL8, lipid metabolism, diet-induced obesity, nonhuman primate model
- MeSH terms
- Animals, Female, Fibroblast Growth Factors, Gene Expression Regulation, Humans, Macaca mulatta, Male, Weight Loss, Gene Expression Profiling, Subcutaneous Fat, Lipogenesis, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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