A Genetic Model to Study the Contribution of Brown and Brite Adipocytes to Metabolism
Open accessAbstract
UCP1-dependent thermogenesis is studied to define new strategies to ameliorate obesity and type 2 diabetes; however, animal models are mostly limited to germline mutations of UCP1, which can effect adaptive changes in UCP1-independent pathways. We develop an inducible mouse model for the sequential ablation of UCP1 + brown and brite/beige adipocytes in adult mice. We demonstrate that activated brown adipocytes can increase systemic energy expenditure (EE) by 30%, while the contribution of brite/beige UCP1 + cells is <5%. Notably, UCP1 + adipocytes do not contribute to circulating FGF21 levels, either at room temperature or after cold exposure. We demonstrate that the FGF21-mediated effects on EE and glucose homeostasis are partially dependent on the presence of UCP1 + cells, while the effect on weight loss is not. In conclusion, acute UCP1 + cell deletion may be a useful model to study the impact of brown and brite/beige adipocytes on metabolism.
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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 [75]
In mice with acute ablation of thermogenic adipose tissues, FGF21 causes no increase in energy expenditure but still increased weight loss through increased physical activity and a trend towards decreased food intake.
“mice with acute ablation of thermogenic adipose tissues exhibited no increase in energy expenditure but still exhibited increased weight loss through increased physical activity and a trend towards decreased food intake75.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [75]
FGF21 significantly decreases body weight to the same extent in wild-type mice and mice acutely lacking thermogenic adipose tissues.
“FGF21 significantly decreased body weight to the same extent in wild-type mice and mice acutely lacking thermogenic adipose tissues.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [75]
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References 41 · Cited by 42
- Authors
- Challa, T. D., Dapito, D. H., Kulenkampff, E., Kiehlmann, E., Moser, C., Straub, L., Sun, W., & Wolfrum, C.
- Affiliations
- ETH Zurich (CH)
- Corresponding author
- Wolfrum, Christian
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 30
- Issue
- 10
- Pages
- 3424-3433.e4
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3010791590
- Cited by
- 42
- References
- 41
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 1 · 2022: 12 · 2021: 12 · 2020: 3
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ETH Zürich Research Collection (cc-by)
- Funders
- Eli Lilly and Company
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- brown adipocytes, beige adipocytes, UCP1, thermogenesis, energy expenditure, FGF21, glucose homeostasis, obesity, type 2 diabetes, cold exposure, weight loss
- MeSH terms
- Adipocytes, Beige, Uncoupling Protein 1, Animals, Energy Metabolism, Fibroblast Growth Factors, Mice, Inbred C57BL, Models, Genetic, Temperature, Gene Deletion, Adipocytes, Brown
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