Pnpla2-KO Mouse

Pnpla2, also known as adipose triglyceride lipase (ATGL) and pigment epithelium-derived factor receptor (PEDF-R), is a key enzyme in lipid metabolism. It is involved in triglyceride hydrolysis and lipid-droplet homeostasis in mice and humans, playing a vital role in processes like intracellular lipolysis, releasing fatty acids from triacylglycerol stores for energy production [2,8].

In human hepatoma cells, siRNA inhibition of Pnpla2 reduced intracellular triglyceride hydrolysis and decreased the secretion of triglyceride-rich lipoproteins (TRLs), but had no effect on lipid-droplet homeostasis, which is different from its function in non-hepatic tissues [1]. In mice, ablation of Pnpla2 (PEDF-R) led to photoreceptor degeneration, with deformities in photoreceptors, changes in phospholipid composition, and compromised photoreceptor function [4]. Also, the absence of Pnpla2 in mouse eyes caused a significant accumulation of lipid droplets in retinal pigment epithelium (RPE) cells, declined electroretinography (ERG) response, and delayed dark adaptation, suggesting its role as a retinyl ester (RE) hydrolase in the RPE and an essential component of the visual cycle [6].

In conclusion, Pnpla2 is crucial for lipid metabolism, with functions in triglyceride hydrolysis, lipoprotein secretion, and phospholipid metabolism in different tissues. Mouse models with Pnpla2 knockout have revealed its significance in photoreceptor structure and function, as well as in the visual cycle. Mutations in Pnpla2 are associated with neutral lipid storage diseases, highlighting its importance in understanding related disease mechanisms [3,5,7].