ArticleMolecular metabolism2018
Molecular elements in FGF19 and FGF21 defining KLB/FGFR activity and specificity.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- [Fibroblast growth factor 21 improves alcoholic liver disease by regulating gut microbiota in mice].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Aerobic Exercise Combined with Multisensory Stimulation Training Improves Cognitive Frailty by Modulating Circulating Klotho.International journal of molecular sciences · 2026Article
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- FGF21 Alleviates Hypoxic-Ischemic White Matter Injury in Neonatal Mice by Mediating Inflammation and Oxidative Stress Through PPAR-γ Signaling Pathway.Molecular neurobiology · 2025Article
- Computer-aided engineering of stabilized fibroblast growth factor 21.Computational and structural biotechnology journal · 2024Article
- The SGLT2 inhibitor Empagliflozin promotes post-stroke functional recovery in diabetic mice.Cardiovascular diabetology · 2024Article
- Size matters: the biochemical logic of ligand type in endocrine crosstalk.Life metabolism · 2024Article
- Non-alcoholic fatty liver disease promotes breast cancer progression through upregulated hepatic fibroblast growth factor 21.Cell death & disease · 2024Article
- Exploring endocrine FGFs - structures, functions and biomedical applications.International journal of biochemistry and molecular biology · 2024Review
- The Novel Tetra-Specific Drug C-192, Conjugated Using UniStac, Alleviates Non-Alcoholic Steatohepatitis in an MCD Diet-Induced Mouse Model.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Analysis of Functional Promoter of Camel FGF21 Gene and Identification of Small Compounds Targeting FGF21 Protein.Veterinary sciences · 2023Article
- Reduction of Plasma BCAAs following Roux-en-Y Gastric Bypass Surgery Is Primarily Mediated by FGF21.Nutrients · 2023Article
- Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions.Nature reviews. Nephrology · 2023Review
- Localization of FGF21 Protein and Lipid Metabolism-Related Genes in Camels.Life (Basel, Switzerland) · 2023Article
- Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency.Scientific reports · 2023Article
- Hepatocyte-specific fibroblast growth factor 21 overexpression ameliorates high-fat diet-induced obesity and liver steatosis in mice.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Potential of Hibiscus sabdariffa Linn. in managing FGF21 resistance in diet-induced-obesity rats via miR-34a regulation.Veterinary medicine and science · 2022Article
- The Saga of Endocrine FGFs.Cells · 2021Review
- FGF19 and FGF21: In NASH we trust.Molecular metabolism · 2021Review
- Glucagon receptor signaling regulates weight loss via central KLB receptor complexes.JCI insight · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo signal, FGF19 and FGF21 require co-receptor βKlotho (KLB) to act in concert with FGF receptors, and yet there is appreciable variance in the C-terminal sequences of these two novel metabolic hormones where binding is believed to be primary. We seek to determine the functional consequences for these amino acid differences and determine whether such information can be used to design high potency antagonists and agonists.
methodsWe employed a functional in vitro assay to identify C-terminal protein fragments capable of fully blocking KLB-mediated FGF19 and 21 receptor signaling. The key residues in each hormone responsible for support full bioactivity were identified through peptide-based Ala-scanning. Chemical optimization of the peptides was employed to increase their antagonistic potency. An optimized sequence as a substituted part of a full length FGF21 was assessed for enhanced FGFR/KLB-mediated agonism using tissue culture and obese mice.
resultsC-terminal FGF19 and FGF21 peptides of relatively short length were observed to potently inhibit the activity of these two hormones, in vitro and in vivo. These FGFs of different sequence also demonstrated a striking conservation of structural determinants to maintain KLB binding. A single C-terminal amino acid in FGF19 was observed to modulate relative activity through FGFR1 and FGFR4. The substitution of native FGF21 C-terminal sequence with a peptide optimized for the highest antagonistic activity resulted in significantly enhanced FGF potency, as measured by in vitro signaling and improvements in metabolic outcomes in diet-induced obese mice.
conclusionsWe report here the ability of short C-terminal peptides to bind KLB and function as antagonists of FGF19 and 21 actions. These proteins maintain high conservation of sequence in those residues central to KLB binding. An FGF21 chimeric protein possessing an optimized C-terminal sequence proved to be a super-agonist in delivery of beneficial metabolic effects in obese mice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.