ArticleMolecular metabolism2017
FGF21 mimetic antibody stimulates UCP1-independent brown fat thermogenesis via FGFR1/βKlotho complex in non-adipocytes.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 55 citations in OpenAlex.
- Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.Proceedings of the National Academy of Sciences of the United States of America · 2020Trial
- Review
- Enhanced metabolic benefits of dietary methionine restriction in cold resistant hybrid UCP1-deficient mice.The Journal of nutritional biochemistry · 2026Article
- Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain.Cell reports · 2026Article
- Fibroblast Growth Factor 21: Mechanisms, Therapeutic Potential, and Clinical Translation in Metabolic Dysfunction.Drug design, development and therapy · 2026Review
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Molecular mechanisms of UCP1-independent thermogenesis: the role of futile cycles in energy dissipation.Journal of physiology and biochemistry · 2025Review
- Brown and beige adipose tissue-derived metabokine and lipokine inter-organ signalling in health and disease.Experimental physiology · 2025Review
- Hepato-cardiac interorgan communication controls cardiac hypertrophy via combined endocrine-autocrine FGF21 signaling.Cell reports. Medicine · 2025Article
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Soluble alpha-klotho and 25-hydroxivitamin D are not associated with brown adipose tissue metabolism in young healthy adults.Journal of physiology and biochemistry · 2025Article
- Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men.Nature metabolism · 2025Article
- Therapeutic effects of FGF21 mimetic bFKB1 on MASH and atherosclerosis in Ldlr-/-.Leiden mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Treatment with dapagliflozin increases FGF-21 gene expression and reduces triglycerides content in myocardial tissue of genetically obese mice.Journal of endocrinological investigation · 2024Article
- Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans WithJournal of the Endocrine Society · 2024Article
- Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network.Genes & diseases · 2024Review
- Brown adipose tissue CoQ deficiency activates the integrated stress response and FGF21-dependent mitohormesis.The EMBO journal · 2024Article
- 360-Degree Perspectives on Obesity.Medicina (Kaunas, Lithuania) · 2023Review
- Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice.Nature metabolism · 2022Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveFibroblast Growth Factor 21 (FGF21) is a potent stimulator of brown fat thermogenesis that improves insulin sensitivity, ameliorates hepatosteatosis, and induces weight loss by engaging the receptor complex comprised of Fibroblast Growth Factor Receptor 1 (FGFR1) and the requisite coreceptor βKlotho. Previously, recombinant antibody proteins that activate the FGFR1/βKlotho complex were proposed to act as an FGF21-mimetic; however, in vivo action of these engineered proteins has not been well studied.
methodsWe investigated the mechanism by which anti-FGFR1/βKlotho bispecific antibody (bFKB1) stimulates thermogenesis in UCP1-expressing brown adipocytes using genetically engineered mice. Anti-FGFR1 agonist antibody was also used to achieve brown adipose tissue restricted activation in transgenic mice.
resultsStudies with global Ucp1-deficient mice and adipose-specific Fgfr1 deficient mice demonstrated that bFKB1 acts on targets distal to adipocytes and indirectly stimulates brown adipose thermogenesis in a UCP1-independent manner. Using a newly developed transgenic system, we also show that brown adipose tissue restricted activation of a transgenic FGFR1 expressed under the control of Ucp1 promoter does not stimulate energy expenditure. Finally, consistent with its action as a FGF21 mimetic, bFBK1 suppresses intake of saccharin-containing food and alcohol containing water in mice.
conclusionsCollectively, we propose that FGFR1/βKlotho targeted therapy indeed mimics the action of FGF21 in vivo and stimulates UCP1-independent brown fat thermogenesis through receptors outside of adipocytes and likely in the nervous system.
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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.