Cited by 95Fibroblast Growth Factor ResearchAdipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and Obesity

Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans

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Baruch, Amos, Wong, Chin, Chinn, Leslie W., Vaze, Anjali, Sonoda, Junichiro, Gelzleichter, Thomas, Chen, Shan, Lewin-Koh, Nicholas +7 more·2020·Proceedings of the National Academy of Sciences

Abstract

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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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.
Venue
Proceedings of the National Academy of Sciences
Published
2020-11-02
Volume
117
Issue
46
Pages
28992-29000
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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