Regulation of lipid droplet homeostasis by hypoxia inducible lipid droplet associated HILPDA

Nearly all cell types have the ability to store excess energy as triglycerides in specialized organelles called lipid droplets. The formation and degradation of lipid droplets is governed by a diverse set of enzymes and lipid droplet-associated proteins. One of the lipid droplet-associated proteins is Hypoxia Inducible Lipid Droplet Associated (HILPDA). HILPDA was originally discovered in a screen to identify novel hypoxia-inducible proteins. Apart from hypoxia, levels of HILPDA are induced by fatty acids and adrenergic agonists. HILPDA is a small protein of 63 amino acids in humans and 64 amino acids in mice. Inside cells, HILPDA is located in the endoplasmic reticulum and around lipid droplets. Gain- and loss-of-function experiments have demonstrated that HILPDA promotes lipid storage in hepatocytes, macrophages and cancer cells. HILPDA increases lipid droplet accumulation at least partly by inhibiting triglyceride hydrolysis via ATGL and stimulating triglyceride synthesis via DGAT1. Overall, HILPDA is a novel regulatory signal that adjusts triglyceride storage and the intracellular availability of fatty acids to the external fatty acid supply and the capacity for oxidation.