FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
Open accessAbstract
Fibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT) temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.
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Mice with acute ablation of UCP1+ adipocytes or lacking UCP1 exhibit impaired FGF21-mediated regulation of glucose homeostasis.
“mice with acute ablation of UCP1+ adipocytes75 or those lacking UCP1 exhibit impaired FGF21-mediated regulation of glucose homeostasis76.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [76]
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- Authors
- Kwon, M. M., O’Dwyer, S. M., Baker, R. K., Covey, S. D., & Kieffer, T. J.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Kieffer, Timothy J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 13
- Issue
- 8
- Pages
- 1521-1527
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2203504182
- Cited by
- 77
- References
- 13
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 10 · 2022: 6 · 2021: 13 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 9 · 2016: 10
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- FGF21, UCP1, glucose clearance, glucose homeostasis, brown adipose tissue, thermogenesis, UCP1 knockout mice, obesity, adipose tissue, weight loss
- MeSH terms
- Uncoupling Protein 1, Animals, Body Weight, Adipose Tissue, Brown, Energy Metabolism, Fibroblast Growth Factors, Glucose, Ion Channels, Male, Obesity, Mice, Knockout, Thermogenesis, Mitochondrial Proteins, Mice, Adipose Tissue, White
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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