A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion
Open accessAbstract
The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion.
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Fgf15 can signal through the brain to modulate glucose homeostasis and glucagon secretion.
“Importantly, Fgf15 can also signal through the brain to modulate glucose homeostasis 45 and glucagon secretion 46.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [46]
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- Authors
- Picard, A., Soyer, J., Berney, X., Tarussio, D., Quenneville, S., Jan, M., Grouzmann, E., Burdet, F., Ibberson, M., & Thorens, B.
- Affiliations
- University of Lausanne (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Thorens, Bernard
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 17
- Issue
- 7
- Pages
- 1795-1806
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5120348
- OpenAlex
- W2556766149
- Cited by
- 35
- References
- 54
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- IRIS (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Swiss National Science Foundation (3100A0B-128657, CRSII3-136201)
- European Research Council (268946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- FGF15, glucagon secretion, hypothalamus, dorsomedial hypothalamus, perifornical area, FGF19, dorsomedial medulla, parasympathetic neurons, quantitative trait loci, recombinant inbred mouse strains, chromosome 7, glucose homeostasis
- MeSH terms
- Aging, Animals, Deoxyglucose, Fibroblast Growth Factors, Genetic Testing, Glucagon, Hypothalamus, Mice, Inbred C57BL, Parasympathetic Nervous System, Genome, Gene Silencing, Chromosomes, Mammalian, Quantitative Trait Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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