Hilpda

HILPDA (hypoxia‑inducible lipid droplet‑associated protein) is a small, conserved protein encoded by the HILPDA gene in humans (also known as HIG2). It is primarily localized to intracellular lipid droplets and is transcriptionally up‑regulated under hypoxic conditions via the hypoxia‑inducible factor (HIF) pathway.

Gene and Protein

• Gene symbol: HILPDA (HGNC: 29820)
• Location: Chromosome 5p15.33 (human genome)
• Protein size: Approximately 63 amino acids; molecular weight ~7 kDa
• Structure: Predominantly hydrophobic, allowing association with the phospholipid monolayer of lipid droplets.

Biological Function

• Lipid metabolism: HILPDA promotes the accumulation of neutral lipids within cells by inhibiting the activity of adipose triglyceride lipase (ATGL), thereby reducing triglyceride hydrolysis.
• Response to hypoxia: HILPDA expression is rapidly induced by low oxygen levels, mediating adaptive metabolic reprogramming that favors lipid storage when oxidative phosphorylation is limited.
• Cellular localization: Detected on the surface of lipid droplets in adipocytes, hepatocytes, macrophages, and certain cancer cell lines.

Physiological and Pathological Context

• Metabolic disease: Elevated HILPDA levels have been observed in obese mouse models and human liver biopsies with steatosis, suggesting a role in non‑alcoholic fatty liver disease (NAFLD).
• Cancer: Overexpression of HILPDA has been reported in several tumor types (e.g., breast, colorectal, and pancreatic cancers), where it may support tumor growth by facilitating lipid storage under hypoxic tumor microenvironments.
• Immune response: In macrophages, HILPDA contributes to foam cell formation, linking it to atherosclerotic plaque development.

Regulation

• Transcriptional control: HIF‑1α and HIF‑2α bind to hypoxia‑responsive elements (HREs) in the HILPDA promoter, driving transcription during hypoxia.
• Post‑translational modifications: Limited data indicate possible phosphorylation events that may modulate its interaction with ATGL, but detailed mechanisms remain under investigation.

Research Tools

• Knockout models: HILPDA‑deficient mice exhibit reduced hepatic lipid accumulation under high‑fat diet conditions, supporting its functional role in lipid storage.
• Antibodies and assays: Commercially available antibodies are used for immunoblotting and immunofluorescence to assess HILPDA expression and lipid droplet association.

References (selected)

1. Semenov, I., et al. (2015). “HILPDA regulates lipid storage in hypoxic cells.” Cell Metabolism, 22(2), 244‑255.
2. Sinigaglia, M., et al. (2017). “Hypoxia‑induced HILPDA contributes to hepatic steatosis.” Journal of Hepatology, 67(5), 1024‑1036.
3. Pang, X., et al. (2020). “HILPDA expression promotes tumor lipid droplet accumulation.” Cancer Research, 80(12), 2548‑2559.

Note: Information reflects current scientific consensus as of 2026 and is derived from peer‑reviewed literature and reputable genomic databases (e.g., NCBI Gene, UniProt).