ArticleThe Journal of comparative neurology2019
The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform.
Article in The Journal of comparative neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Liver Brain Interactions: Focus on FGF21 a Systematic Review.International journal of molecular sciences · 2022Pooled it
- Tanycytes: bloodhounds of the metabolic brain.Trends in endocrinology and metabolism: TEM · 2026Review
- Hypothalamus-liver talks: whispers in the language of metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- FGF21 signals through hindbrain neurons to alter food intake and energy expenditure during dietary protein restriction.Cell reports · 2026Article
- Glucagon-Like Peptide-1 Targets in the Human Nodose Ganglion.The Journal of comparative neurology · 2026Article
- Negative feedback regulation of alcohol ingestion through the FGF21-PVH oxytocin-VTA dopamine system.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes.Pharmacological research · 2026Review
- The liver-brain axis, from its function to preventive therapeutic strategies in diseases.Frontiers in endocrinology · 2026Review
- Free fatty acid receptor 4 modulates dietary sugar preference via the gut microbiota.Nature microbiology · 2025Article
- Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH.Gastro hep advances · 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
- FGF21 as a mediator of adaptive changes in food intake and macronutrient preference in response to protein restriction.Neuropharmacology · 2024Review
- FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.bioRxiv : the preprint server for biology · 2024Article
- Metabolic Crosstalk between Liver and Brain: From Diseases to Mechanisms.International journal of molecular sciences · 2024Review
- Hepatic interoception in health and disease.Autonomic neuroscience : basic & clinical · 2024Review
- A human laboratory study on the link between alcohol administration and circulating fibroblast growth factor 21 (FGF21) in individuals with alcohol use disorder.Drug and alcohol dependence · 2023Article
- Reduction of Plasma BCAAs following Roux-en-Y Gastric Bypass Surgery Is Primarily Mediated by FGF21.Nutrients · 2023Article
- FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system.Cell metabolism · 2023Article
- Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins.Cell metabolism · 2023Article
- Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models of obesity and diabetes. The current work was undertaken to advance our understanding of the receptor expression, as sites of ligand action by FGF19, FGF21, and FGF1 in the mammalian brain remains unresolved. Recent advances in automated RNAscope in situ hybridization and droplet digital PCR (ddPCR) technology allowed us to interrogate central FGFR/beta klotho (Klb) system at the cellular level in the mouse, with relevant comparisons to nonhuman primate and human brain. FGFR1-3 gene expression was broadly distributed throughout the CNS in Mus musculus, with FGFR1 exhibiting the greatest heterogeneity. FGFR4 expression localized only in the medial habenula and subcommissural organ of mice. Likewise, Klb mRNA was restricted to the suprachiasmatic nucleus (SCh) and select midbrain and hindbrain nuclei. ddPCR in the rodent hypothalamus confirmed that, although expression levels are indeed low for Klb, there is nonetheless a bonafide subpopulation of Klb+ cells in the hypothalamus. In NHP and human midbrain and hindbrain, Klb + cells are quite rare, as is expression of FGFR4. Collectively, these data provide the most robust central map of the FGFR/Klb system to date and highlight central regions that may be of critical importance to assess central ligand effects with pharmacological dosing, such as the putative interactions between the endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.
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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.