Pla2g12b, Phospholipase A2 group 12B, is involved in lipid-related biological processes. It channels lipids within the endoplasmic reticulum lumen into nascent lipoproteins, promoting efficient lipid secretion and preventing intracellular lipid excess. It also participates in pathways like arachidonic acid metabolism and is associated with lipoprotein homeostasis, which is crucial for normal physiological functions [1,2]. Genetic mouse models are valuable for studying Pla2g12b.

In Pla2g12b mutant mice, profound resistance to atherosclerosis was detected, suggesting an evolutionary trade-off between triglyceride transport and cardiovascular disease risk [1]. In a membranous nephropathy (MN) mouse model, AA metabolites were activated, and the expression of Pla2g12b and NF-κB pathway levels were elevated. In cellular experiments, Pla2g12B promoted apoptosis and suppressed cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors [2]. Mice with mutated Pla2g12b had reduced HDL cholesterol, non-HDL cholesterol, and triglyceride levels [3]. In Pla2g12b-null mice, ERRγ failed to regulate hepatic VLDL-TG secretion, and there was an accumulation of large lipid droplets in the liver [4].

In conclusion, Pla2g12b plays essential roles in lipid metabolism, especially in triglyceride-rich lipoprotein expansion and arachidonic acid metabolism. The study of Pla2g12b KO/CKO mouse models has revealed its significance in diseases such as atherosclerosis, membranous nephropathy, and in regulating lipoprotein-related lipid levels. These findings contribute to understanding the mechanisms underlying these diseases and may offer potential therapeutic targets [1,2,3,4].

References:

1. Thierer, James H, Foresti, Ombretta, Yadav, Pradeep Kumar, Hussain, M Mahmood, Farber, Steven A. 2024. Pla2g12b drives expansion of triglyceride-rich lipoproteins. In Nature communications, 15, 2095. doi:10.1038/s41467-024-46102-4. https://pubmed.ncbi.nlm.nih.gov/38453914/

2. Fu, Linlin, Ping, Jinliang, Guo, Fei, Luo, Mingjun, Chen, Lijing. 2023. PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy. In Kidney & blood pressure research, 48, 652-665. doi:10.1159/000533805. https://pubmed.ncbi.nlm.nih.gov/37757774/

3. Aljakna, Aleksandra, Choi, Seungbum, Savage, Holly, Hibbs, Matt, Korstanje, Ron. 2012. Pla2g12b and Hpn are genes identified by mouse ENU mutagenesis that affect HDL cholesterol. In PloS one, 7, e43139. doi:10.1371/journal.pone.0043139. https://pubmed.ncbi.nlm.nih.gov/22912808/

4. Chen, Longhui, Wu, Min, Zhang, Shengnan, Chen, Ling, Qu, Linbing. 2019. Estrogen-related receptor γ regulates hepatic triglyceride metabolism through phospholipase A2 G12B. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 7942-7952. doi:10.1096/fj.201802704R. https://pubmed.ncbi.nlm.nih.gov/30922124/