TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue
Open accessAbstract
Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 +/+ mice but not in their Tgr5 −/− littermates. This phenotype is recapitulated in vitro in differentiated adipocytes, in which TGR5 activation increases free fatty acid availability through lipolysis, hence fuelling β-oxidation and thermogenic activity. TGR5 signalling also induces mitochondrial fission through the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken together, these data identify TGR5 as a druggable target to promote beiging with potential applications in the management of metabolic disorders.
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TGR5 adipose tissue-specific knockout mice show neglectable browning and exhibit reduced cold tolerance due to reduced adipose mitochondrial fusion.
“These mice show neglectable browning and exhibit reduced cold tolerance due to reduced adipose mitochondrial fusion 98.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [98]
Studies using BA receptor TGR5 adipose tissue-specific knockout mice proved that BAs also participate in the browning of WAT.
“Moreover, studies using BA receptor TGR5 adipose tissue‐specific knockout mice proved that BAs also participate in the browning of WAT.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [98]
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- Authors
- Velazquez-Villegas, L. A., Perino, A., Lemos, V., Zietak, M., Nomura, M., Pols, T. W. H., & Schoonjans, K.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Universidade do Porto (PT)
- Corresponding author
- Schoonjans, Kristina
- Venue
- Nature Communications
- Published
- 2018-01-16
- Volume
- 9
- Issue
- 1
- Pages
- 245-245
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5770450
- OpenAlex
- W2783262542
- Cited by
- 268
- References
- 71
- Citations by year
- 2026: 29 · 2025: 35 · 2024: 42 · 2023: 38 · 2022: 30 · 2021: 26 · 2020: 31 · 2019: 24 · 2018: 13
- FWCI
- 16.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (125487)
- Fundacja na rzecz Nauki Polskiej
- Consejo Nacional de Ciencia y Tecnología
- Fundação para a Ciência e a Tecnologia (SFRH/BD/52046/2012)
- 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
- TGR5, G protein-coupled bile acid receptor, white adipose tissue, beige adipose tissue, brown adipose tissue, mitochondrial fission, mitochondrial dynamics, Drp1, ERK signaling, thermogenesis, lipolysis, free fatty acids, fatty acid beta-oxidation, mitochondrial respiration, cold exposure, high-fat diet, adiposity, thermoneutrality
- MeSH terms
- Adipose Tissue, Beige, Adipocytes, Beige, Animals, Cell Differentiation, Cell Line, Fatty Acids, Nonesterified, Humans, Temperature, Signal Transduction, Mice, Knockout, 3T3-L1 Cells, Receptors, G-Protein-Coupled, Subcutaneous Fat, Mice, Adipose Tissue, White, Adipocytes, White, Mitochondrial Dynamics
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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