Osbpl8, also known as ORP8 (Oxysterol Binding Protein-related protein 8), is an endoplasmic reticulum sterol sensor involved in cellular lipid metabolism [2,3]. It belongs to the oxysterol binding protein (OSBP) family, which are implicated in sterol homeostasis, vesicular trafficking, and other functions [3]. ORP8 can act as a lipophagy receptor, mediating the encapsulation of lipid droplets (LDs) by autophagosomal membranes for lysosomal degradation, a process crucial for lipid and energy homeostasis [1].

In Osbpl8 -/- (KO) mouse models, male mice on chow diet showed a marked elevation of high-density lipoprotein (HDL) cholesterol and phospholipids, while female KO mice had a less prominent increase [2]. Additionally, female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while male KO mice displayed elevated plasma cholesterol biosynthetic markers [2]. Deletion of ORP8 in mice led to accumulation of LDs and increased intracellular triglyceride, as well as liver lipid clearance defects, indicating its key role in lipid metabolism [1].

In conclusion, Osbpl8 is essential for maintaining lipid and energy homeostasis through its role in lipophagy. The Osbpl8 KO mouse models have revealed its significant impact on lipid metabolism, particularly in relation to HDL levels and gender-specific lipid-related phenotypes, providing insights into potential mechanisms underlying lipid-related diseases [1,2].

References:

1. Pu, Maomao, Zheng, Wenhui, Zhang, Hongtao, Neculai, Dante, Liu, Wei. . ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover. In Protein & cell, 14, 653-667. doi:10.1093/procel/pwac063. https://pubmed.ncbi.nlm.nih.gov/37707322/

2. Béaslas, Olivier, Metso, Jari, Nissilä, Eija, Jauhiainen, Matti, Olkkonen, Vesa M. 2013. Osbpl8 deficiency in mouse causes an elevation of high-density lipoproteins and gender-specific alterations of lipid metabolism. In PloS one, 8, e58856. doi:10.1371/journal.pone.0058856. https://pubmed.ncbi.nlm.nih.gov/23554939/

3. Santos, Nina Criado, Girik, Vladimir, Nunes-Hasler, Paula. 2020. ORP5 and ORP8: Sterol Sensors and Phospholipid Transfer Proteins at Membrane Contact Sites? In Biomolecules, 10, . doi:10.3390/biom10060928. https://pubmed.ncbi.nlm.nih.gov/32570981/