Abstract
Lipid storage droplet protein 5 (LSDP5) is a lipid droplet-associated protein of the PAT (perilipin, adipophilin, and TIP47) family that is expressed in the liver in a peroxisome proliferator-activated receptor alpha (PPARα)-dependent manner; however, its exact function has not been elucidated. We noticed that LSDP5 was localized to the surface of lipid droplets in hepatocytes. Overexpression of LSDP5 enhanced lipid accumulation in the hepatic cell line AML12 and in primary hepatocytes. Knock-down of LSDP5 significantly decreased the triglyceride content of lipid droplets, stimulated lipolysis, and modestly increased the mitochondrial content and level of fatty-acid β-oxidation in the mitochondria. The expression of PPARα was increased in LSDP5-deficient cells and required for the increase in the level of fatty acid β-oxidation in LSDP5-deficient cells. Using serial deletions of LSDP5, we determined that the lipid droplet-targeting domain and the domain directing lipid droplet clustering overlapped and were localized to the 188 amino acid residues at the N-terminus of LSDP5. Our findings suggest that LSDP5, a novel lipid droplet protein, may contribute to triglyceride accumulation by negatively regulating lipolysis and fatty acid oxidation in hepatocytes.
Highlights
Obesity occurs because of an imbalance between energy intake and expenditure
Similar to other members of the PAT family, the expression of Lipid storage droplet protein 5 (LSDP5) is regulated by peroxisome proliferator-activated receptor a (PPARa), a ligand-activated transcription factor belonging to the nuclear receptor superfamily [6,11,12,13,15]
LSDP5 co-localized with enhanced green fluorescent protein (EGFP)adipophilin, which is a well-recognized marker of lipid droplets
Summary
Obesity occurs because of an imbalance between energy intake and expenditure. Most excess energy is stored as triglycerides (TGs) in lipid droplets in adipose tissue. The best characterized lipid droplet-associated protein is perilipin, which shares sequence similarity with two other lipid droplet-associated proteins, adipophilin/adipocyte differentiationrelated protein (ADRP) and tail-interacting protein 47 (TIP47). Together, these proteins form the PAT (perilipin-adipophilinTIP47) family of proteins, and S3-12 has recently been classified in this family [6]. The initial identifications and characterizations of LSDP5 as a lipid droplet-binding protein were reported by three independent groups, who named the protein myocardial lipid droplet protein (MLDP), oxidative tissueenriched PAT protein (OXPAT), and LSDP5 [11,12,13] These studies reported that LSDP5 is ubiquitously expressed in tissues that exhibit high levels of fatty acid oxidation, including the heart, skeletal muscle, and liver. The mechanisms by which LSDP5 promotes the lipid accumulation are mostly unknown
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