FGF19 — Fibroblast Growth Factor 19

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gene1001 wordssynced 2026-04-02

FGF19 — Fibroblast Growth Factor 19

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FGF19 — Fibroblast Growth Factor 19</th>
</tr>
<tr>
<td class="label">:---</td>
<td>:---</td>
</tr>
<tr>
<td class="label">Symbol</td>
<td>FGF19</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Fibroblast Growth Factor 19</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2259</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9KUM4</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000162337</td>
</tr>
<tr>
<td class="label">Factor</td>
<td>Primary Site</td>
</tr>
<tr>
<td class="label">:---</td>
<td>:---</td>
</tr>
<tr>
<td class="label">FGF19</td>
<td>Small intestine</td>
</tr>
<tr>
<td class="label">FGF21</td>
<td>Liver, adipose</td>
</tr>
<tr>
<td class="label">FGF23</td>
<td>Bone</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cirrhosis" style="color:#ef9a9a">Cirrhosis</a>, <a href="/wiki/depression" style="color:#ef9a9a">Depression</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">48 edges</a></td>
</tr>
</table>

...

FGF19 — Fibroblast Growth Factor 19

Overview

FGF19 (Fibroblast Growth Factor 19) is a member of the endocrine subfamily of fibroblast growth factors (FGFs) that functions as a metabolic regulator. Unlike classic FGFs that act locally, FGF19 functions in an endocrine manner, traveling from its site of production (small intestine) to regulate metabolic processes in the liver and other tissues. It signals through the FGF receptor FGFR4, with Klothos (KL) as the required co-receptor.

Normal Function

Endocrine Signaling

FGF19 is one of the "metabolic FGFs" (along with FGF21 and FGF23) that act as endocrine factors, regulating systemic metabolism. Unlike the canonical FGFs (FGF1-FGF10), these metabolic FGFs have low heparin-binding affinity, allowing them to enter circulation.

The endocrine FGF signaling pathway:

Production: FGF19 is expressed in the small intestine (ileum), particularly in enterocytes

Secretion: Secreted into portal circulation

Receptor binding: Binds to FGFR4 (FGF Receptor 4) on target cells

Co-receptor requirement: Requires Klotho (KL) for signaling

Metabolic effects: Regulates bile acid synthesis, glucose metabolism, and energy expenditure

FGFR4 Signaling

FGF19 binds specifically to FGFR4, a receptor tyrosine kinase expressed predominantly in the liver. The signaling cascade involves:

FGF19 → FGFR4 → FRS2 → RAS/MAPK pathway
Activation of downstream pathways including PI3K/AKT and MAPK/ERK
Regulation of gene expression in hepatocytes

FGFR4 is the only FGFR that can respond to FGF19, providing tissue-specific signaling. This specificity makes the FGF19-FGFR4 axis an attractive therapeutic target.

Metabolic Regulation

FGF19 regulates several metabolic processes:

Bile Acid Homeostasis

Suppresses cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis
Reduces hepatic bile acid production
Feedback regulation of bile acid levels

Glucose Metabolism

Improves insulin sensitivity
Reduces hepatic glucose production
Promotes glucose uptake in peripheral tissues

Energy Expenditure

Increases metabolic rate
Promotes weight loss in obesity models
Increases fatty acid oxidation

Lipid Metabolism

Reduces hepatic triglyceride accumulation
Improves lipid profiles

Disease Associations

Metabolic Disorders

FGF19 is primarily associated with metabolic diseases:

Obesity and Type 2 Diabetes

FGF19 signaling is dysregulated in obesity
Therapeutic potential for metabolic syndrome
Recombinant FGF19 analogs are in development

Non-Alcoholic Fatty Liver Disease (NAFLD)

FGF19 modulates hepatic lipid accumulation
May protect against steatosis

Dyslipidemia

Effects on cholesterol and triglyceride metabolism

FGF19 in Neurodegeneration: Current Understanding

Direct evidence for FGF19 involvement in neurodegeneration is limited. However, several relevant connections exist:

Metabolic Syndrome and Neurodegeneration

Type 2 diabetes is a risk factor for AD and PD
FGF19 improves insulin sensitivity, potentially benefiting brain health

Bile Acids and Brain Function

Bile acids can cross the blood-brain barrier
Farnesoid X receptor (FXR) signaling in the brain is emerging
FGF19 regulates bile acid production, indirectly affecting brain chemistry

FGF Signaling in the Brain

Other FGFs (FGF2, FGF21) have neuroprotective effects
While FGF19 doesn't signal in the brain directly, systemic metabolic effects could influence neurodegeneration

Cardiovascular Disease

FGF19 affects:

Cardiac function (may have protective effects)
Vascular smooth muscle cell proliferation
Atherosclerosis progression

Expression Pattern

Tissue Distribution

FGF19 expression is highly restricted:

Small intestine (ileum) — primary site
Liver — minimal expression
Colon — low expression

Unlike other FGFs, FGF19 is not significantly expressed in the brain or nervous system. The original page's description of brain expression appears to be incorrect and may reflect confusion with other growth factors.

Regulation

FGF19 expression is regulated by:

Bile acids: Activate FXR in enterocytes, inducing FGF19 expression
Cholesterol: Dietary cholesterol affects expression
Enterohepatic circulation: Bile acid flux regulates transcription

Mermaid Diagram: FGF19 Endocrine Signaling

Mermaid diagram (expand to render)

Comparison with Other Metabolic FGFs

Therapeutic Implications

FGF19 Agonists

Recombinant FGF19 analogs are being developed for:

Obesity: Promote weight loss
Type 2 Diabetes: Improve insulin sensitivity
NAFLD/NASH: Reduce hepatic steatosis

Challenges

FGF19's role in tumors (potential oncogenic effects)
Species-specific activity differences
Safety concerns requiring careful monitoring

Indirect Neurodegeneration Relevance

Targeting FGF19 for metabolic disease could indirectly benefit brain health by:

Improving systemic insulin sensitivity
Reducing neuroinflammation from metabolic dysfunction
Modulating bile acid signaling

Key Research Findings

FGF19-FGFR4 axis: The specific interaction between FGF19 and FGFR4 provides tissue-selective targeting.

Bile acid regulation: FGF19 is the primary endocrine regulator of bile acid synthesis.

Metabolic effects: FGF19 improves glucose homeostasis and promotes energy expenditure.

Therapeutic potential: FGF19 analogs represent novel treatments for metabolic disease.

External Links

[NCBI Gene: FGF19](https://www.ncbi.nlm.nih.gov/gene/2259)
[UniProt: Q9KUM4](https://www.uniprot.org/uniprotkb/Q9KUM4/entry)
[Ensembl: FGF19](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000162337)

References

[FGF19 Gene - NCBI Gene Database](https://www.ncbi.nlm.nih.gov/gene/2259)

[FGF19 - UniProt](https://www.uniprot.org/uniprotkb/Q9KUM4/entry)

[FGF19 signaling through FGFR4 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/14671312/)

[Endocrine FGFs: integrators of energy homeostasis (PubMed)](https://pubmed.ncbi.nlm.nih.gov/23154941/)

[FGF19 and bile acid metabolism (PubMed)](https://pubmed.ncbi.nlm.nih.gov/23555106/)

[FGF19 in metabolic disease (PubMed)](https://pubmed.ncbi.nlm.nih.gov/25983276/)

[FGFR4 in liver disease (PubMed)](https://pubmed.ncbi.nlm.nih.gov/28553993/)

Pathway Diagram

The following diagram shows the key molecular relationships involving FGF19 — Fibroblast Growth Factor 19 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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FGF19 — Fibroblast Growth Factor 19

FGF19 — Fibroblast Growth Factor 19

Overview

FGF19 — Fibroblast Growth Factor 19

Overview

Normal Function

Endocrine Signaling

FGFR4 Signaling

Metabolic Regulation

Disease Associations

Metabolic Disorders

FGF19 in Neurodegeneration: Current Understanding

Cardiovascular Disease

Expression Pattern

Tissue Distribution

Regulation

Mermaid Diagram: FGF19 Endocrine Signaling

Comparison with Other Metabolic FGFs

Therapeutic Implications

FGF19 Agonists

Challenges

Indirect Neurodegeneration Relevance

Key Research Findings

See Also

External Links

References

Pathway Diagram