Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans
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Significance: Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes. Here we show that a bispecific anti-FGFR1/KLB agonist antibody, BFKB8488A, mimics the actions of FGF21 in monkeys and humans. BFKB8488A induced marked weight loss in obese monkeys while elevating expression of FGFR1 target genes in adipose tissue. A clinical study in overweight human participants demonstrated that a single dose of BFKB8488A caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that antibody-mediated activation of the FGFR1/KLB complex in humans recapitulates the effects of FGF21 and can be used as therapy for obesity-related metabolic defects.
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Administration of an FGF21 analogue to people with obesity decreases preference for sweet-tasting food and carbohydrate intake.
“administration of an FGF21 analogue to people with obesity decreases the preference for sweet-tasting food and carbohydrate intake123.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [123]
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CRISPRa‐based activation of Fgf21 and Fndc5 ameliorates obesity by promoting adipocytes browning
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Hypoxia as a Double-Edged Sword to Combat Obesity and Comorbidities
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Fibroblast growth factor 21 and dietary macronutrient intake in female mice
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New Mediators in the Crosstalk between Different Adipose Tissues
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Fibroblast growth factor 21 and dietary interventions: what we know and what we need to know next
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Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans With FGFR1 Mutations
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Fibroblast growth factor-21 improves insulin action in nonlactating ewes
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Therapeutic effects of FGF21 mimetic bFKB1 on MASH and atherosclerosis in Ldlr−/−.Leiden mice
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Treating metabolic dysfunction‐associated steatohepatitis: The fat‐trimming FGF21 approach
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Saponins from Panax japonicus Enhance Lipolysis via Acting on FGF21-β-Klotho/FGFR1 in Obese Mice
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Analytical Characterization of Bispecific Antibodies and Bispecific Molecules
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- Authors
- Baruch, A., Wong, C., Chinn, L. W., Vaze, A., Sonoda, J., Gelzleichter, T., Chen, S., Lewin-Koh, N., Morrow, L., Dheerendra, S., Boismenu, R., Gutierrez, J., Wakshull, E., Wilson, M. E., & Arora, P. S.
- Affiliations
- Genentech (US)
- Genentech Research and Early Development, Genentech, Inc., South San Francisco, CA 94080;
- ProSciento, Inc., Chula Vista, CA 91911
- Corresponding author
- Arora, Puneet S.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-11-02
- Volume
- 117
- Issue
- 46
- Pages
- 28992-29000
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC7682391
- OpenAlex
- W3095442103
- Cited by
- 95
- References
- 47
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 21 · 2023: 11 · 2022: 23 · 2021: 18 · 2020: 2
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Genentech (none)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- FGF21, bispecific antibodies, obesity, metabolic dysfunction, cardiometabolic parameters, adiponectin, food preferences, weight loss, Macaca fascicularis
- MeSH terms
- Adipose Tissue, Adolescent, Adult, Aged, Animals, Antibodies, Body Weight, Female, Fibroblast Growth Factors, Food Preferences, Homeostasis, Humans, Macaca fascicularis, Male, Middle Aged, Obesity, Biomarkers, Weight Loss, Mice, Receptor, Fibroblast Growth Factor, Type 1, Adiponectin, Young Adult
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