FGF19 — Fibroblast Growth Factor 19

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

<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) 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:

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

Metabolic Regulation

FGF19 regulates several metabolic processes:

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

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

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

• Reduces hepatic triglyceride accumulation
• Improves lipid profiles

Disease Associations

Metabolic Disorders

FGF19 is primarily associated with metabolic diseases:

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

• FGF19 modulates hepatic lipid accumulation
• May protect against steatosis

• 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:

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

• 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

• 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

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

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

See Also

• [Fibroblast Growth Factors](/proteins/fgf-family)
• [FGFR4 Signaling](/mechanisms/fgfr-signaling)
• [Metabolic FGFs](/proteins/metabolic-fgfs)
• [Bile Acid Metabolism](/mechanisms/bile-acid-metabolism)
• [Insulin Signaling](/mechanisms/insulin-signaling)
• [Type 2 Diabetes](/diseases/type-2-diabetes)
• [Alzheimer's Disease](/diseases/alzheimers-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

Pathway Diagram

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