ArticleMolecular metabolism2015
Genetic disruption of uncoupling protein 1 in mice renders brown adipose tissue a significant source of FGF21 secretion.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 83 citations in OpenAlex.
- NCOA1 is a gatekeeper of the sexually dimorphic thermogenic activity of white adipose tissue.Nature communications · 2026Article
- Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026Review
- The role of FGF21 in the metabolic adjustments required for exercise capacity.Life sciences · 2025Review
- Brown adipose tissue activity impacts systemic lactate clearance in male mice.The Journal of physiology · 2025Article
- Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue.Nature communications · 2025Article
- Development of an adipocyte differentiation protocol using 3T3-L1 cells for the investigation of the browning process: identification of the PPAR-γ agonist rosiglitazone as a browning reference drug.Frontiers in pharmacology · 2025Article
- Effects of swimming in cold water on lipolysis indicators via fibroblast growth factor-21 in male Wistar rats.Biochemistry and biophysics reports · 2024Article
- Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network.Genes & diseases · 2024Review
- The secretory function of adipose tissues in metabolic regulation.Life metabolism · 2024Review
- Exploring endocrine FGFs - structures, functions and biomedical applications.International journal of biochemistry and molecular biology · 2024Review
- Uncoupling protein 1-driven Cre (bioRxiv : the preprint server for biology · 2023Article
- Hyperphagia of female UCP1-deficient mice blunts anti-obesity effects of FGF21.Scientific reports · 2023Article
- Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat.Molecular metabolism · 2022Article
- The endocrine role of brown adipose tissue: An update on actors and actions.Reviews in endocrine & metabolic disorders · 2022Review
- The potential function and clinical application of FGF21 in metabolic diseases.Frontiers in pharmacology · 2022Review
- Obesity-resistance of UCP1-deficient mice associates with sustained FGF21 sensitivity in inguinal adipose tissue.Frontiers in endocrinology · 2022Article
- The evolving view of thermogenic adipocytes - ontogeny, niche and function.Nature reviews. Endocrinology · 2021Review
- Brown adipocyte ATF4 activation improves thermoregulation and systemic metabolism.Cell reports · 2021Article
- Metabolic Messengers: FGF21.Nature metabolism · 2021Review
- Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine.Evidence-based complementary and alternative medicine : eCAM · 2021Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCirculating fibroblast growth factor 21 (FGF21) is an important auto- and endocrine player with beneficial metabolic effects on obesity and diabetes. In humans, thermogenic brown adipose tissue (BAT) was recently suggested as a source of FGF21 secretion during cold exposure. Here, we aim to clarify the role of UCP1 and ambient temperature in the regulation of FGF21 in mice.
methodsWildtype (WT) and UCP1-knockout (UCP1 KO) mice, the latter being devoid of BAT-derived non-shivering thermogenesis, were exposed to different housing temperatures. Plasma metabolites and FGF21 levels were determined, gene expression was analyzed by qPCR, and tissue histology was performed with adipose tissue.
resultsAt thermoneutrality, FGF21 gene expression and serum levels were not different between WT and UCP1 KO mice. Cold exposure led to highly increased FGF21 serum levels in UCP1 KO mice, which were reflected in increased FGF21 gene expression in adipose tissues but not in liver and skeletal muscle. Ex vivo secretion assays revealed FGF21 release only from BAT, progressively increasing with decreasing ambient temperatures. In association with increased FGF21 serum levels in the UCP1 KO mouse, typical FGF21-related serum metabolites and inguinal white adipose tissue morphology and thermogenic gene expression were altered.
conclusionsHere we show that the genetic ablation of UCP1 increases FGF21 gene expression in adipose tissue. The removal of adaptive nonshivering thermogenesis renders BAT a significant source of endogenous FGF21 under thermal stress. Thus, the thermogenic competence of BAT is not a requirement for FGF21 secretion. Notably, high endogenous FGF21 levels in UCP1-deficient models and subjects may confound pharmacological FGF21 treatments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.