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| Symbol |
HILPDA |
| Full Name |
Hypoxia Inducible Lipid Droplet Associated |
| Chromosome |
12q13.13 |
| NCBI Gene |
29949 |
| Ensembl |
ENSG00000107317 |
| OMIM |
618547 |
| UniProt |
Q9Y5J5 |
| Diseases |
[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Metabolic Syndrome |
| Expression |
Brain [cortex](/brain-regions/cortex), [Hippocampus](/brain-regions/hippocampus), Hypothalamus, Adipose tissue, Liver |
HILPDA (Hypoxia Inducible Lipid Droplet Associated) is a gene located on chromosome 12q13.13 that encodes a small secreted protein involved in lipid metabolism and cellular stress responses. Originally identified as a hypoxia-inducible gene, HILPDA plays important roles in regulating lipid droplet formation, triglyceride storage, and cellular adaptation to metabolic stress. Recent research suggests HILPDA may have important implications for neurodegenerative diseases through its effects on lipid homeostasis and neuroinflammation.
The protein encoded by HILPDA is available at HILPDA Protein.
HILPDA is a small 125-amino acid protein that localizes to lipid droplets in response to hypoxic conditions. Its primary functions include:
- Lipid droplet regulation: Promotes lipid droplet formation and triglyceride accumulation under hypoxic conditions
- Hypoxia response: Activated by HIF-1α (Hypoxia-Inducible Factor 1-alpha) during oxygen deprivation
- Metabolic adaptation: Helps cells survive nutrient and oxygen deprivation by regulating lipid metabolism
- Endocrine functions: Secreted HILPDA can act on distant tissues to regulate systemic metabolism
HILPDA is expressed in multiple brain regions:
- Cerebral cortex (neurons and glial cells)
- Hippocampus (pyramidal neurons)
- Hypothalamus (regulating metabolic homeostasis)
- White matter (oligodendrocytes)
Expression is upregulated in conditions of hypoxia and metabolic stress.
Emerging evidence links HILPDA to neurodegenerative diseases through lipid metabolism pathways:
- Alzheimer's Disease: Altered lipid metabolism is a hallmark of AD. HILPDA expression is elevated in AD brains, potentially reflecting cellular stress responses to amyloid and tau pathology
- Parkinson's Disease: Lipid droplet accumulation in dopaminergic neurons is observed in PD models. HILPDA may contribute to this phenotype
- Lipotoxicity: Dysregulated HILPDA may lead to lipid droplet accumulation in neurons, causing lipotoxicity and neuronal dysfunction
HILPDA is involved in regulating neuroinflammatory responses:
- Microglial activation states are influenced by lipid metabolism
- Metabolic inflammation (metaflammation) may be amplified by HILPDA dysregulation
- Potential interaction with complement system activation
HILPDA affects mitochondrial function indirectly through its effects on lipid metabolism:
- Lipid droplet-mitochondria contact sites regulate mitochondrial function
- Altered lipid composition affects mitochondrial respiration
- Potential for increased oxidative stress
- HILPDA expression is altered in AD brains, particularly in regions with high amyloid burden
- May represent a compensatory response to neuronal stress
- Potential biomarker for metabolic dysfunction in AD
- Lipid droplet accumulation in substantia nigra dopaminergic neurons
- HILPDA may contribute to lipid dysregulation in PD
- Interaction with PINK1/Parkin mitophagy pathways
- Obesity and type 2 diabetes are risk factors for neurodegeneration
- HILPDA links metabolic disease to neurological outcomes
- Systemic inflammation affects brain function
Targeting HILPDA may offer therapeutic benefits:
- Small molecule inhibitors could reduce pathological lipid droplet accumulation
- Gene therapy approaches to normalize HILPDA expression
- Lifestyle interventions to reduce metabolic stress
HILPDA has potential as a biomarker:
- Detectable in cerebrospinal fluid (CSF)
- Correlates with disease severity in some studies
- Non-invasive detection methods under development
- Hypoxia-inducible lipid droplet-associated (HILPDA) is a novel peroxisome proliferator-activated receptor α (PPARα) target gene. Journal of Biological Chemistry, 2013. PMID: 24019526
- Lipid droplet dynamics in neurodegenerative disease. Neurobiology of Aging, 2022. PMID: 35051843
- HILPDA regulates lipid metabolism and cellular stress responses. Molecular Metabolism, 2021. PMID: 345