Pla2g12a, short for phospholipase A2 group XIIA, is a secreted phospholipase involved in lipid metabolism pathways. Secreted phospholipase A2s are generally associated with obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease, indicating its biological importance [1,3,4]. Genetic models such as mouse models can be valuable in studying its functions.

Overexpression of hPLA2G12A in mice using an AAV9 vector led to decreased serum lipid levels in wild-type mice on chow or high-fat diets. It protected against diet-induced obesity and insulin resistance in high-fat-fed mice, by increasing physical activity and energy expenditure rather than through its enzymatic activity. It also induced changes in genes like ApoC2, Cd36, and Angptl8, enhancing the clearance of circulating triglycerides and hepatic uptake of fatty acids [1]. In T cell-specific Pla2g12a-deficient mice, the development of disease was prevented in an experimental autoimmune encephalomyelitis model of multiple sclerosis, as 1-oleoyl-lysophosphatidylethanolamine was reduced in Pla2g12a-deficient TH17 cells, abolishing interleukin-17 production and disrupting TH17 cell differentiation [2]. Knocking-down Pla2g12a expression in cultured vascular endothelial cells or macrophages increased their adhesion to ECs in vitro, suggesting its role in atherosclerosis as an atheroprotective gene in mice [4].

In conclusion, Pla2g12a plays a crucial role in lipid metabolism, energy expenditure, and immune-related cell differentiation. Mouse models, including gene-knockout models, have revealed its significance in conditions like obesity, insulin resistance, multiple sclerosis, and atherosclerosis, providing insights into potential therapeutic targets for these diseases [1,2,4].

References:

1. Wu, Min, Wang, Qian, Li, Hengchun, Chen, Ling, Qu, Linbing. . PLA2G12A protects against diet-induced obesity and insulin resistance by enhancing energy expenditure and clearance of circulating triglycerides. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e23643. doi:10.1096/fj.202302075R. https://pubmed.ncbi.nlm.nih.gov/38703030/

2. Endo, Yusuke, Kanno, Toshio, Nakajima, Takahiro, Murakami, Makoto, Nakayama, Toshinori. 2023. 1-Oleoyl-lysophosphatidylethanolamine stimulates RORγt activity in TH17 cells. In Science immunology, 8, eadd4346. doi:10.1126/sciimmunol.add4346. https://pubmed.ncbi.nlm.nih.gov/37540735/

3. Liu, Zheng-Yu, Liu, Fen, Cao, Yan, Hong, Xiu-Qin, Zheng, Peng-Fei. 2023. ACSL1, CH25H, GPCPD1, and PLA2G12A as the potential lipid-related diagnostic biomarkers of acute myocardial infarction. In Aging, 15, 1394-1411. doi:10.18632/aging.204542. https://pubmed.ncbi.nlm.nih.gov/36863716/

4. Nicolaou, Alexandros, Northoff, Bernd H, Sass, Kristina, Teupser, Daniel, Holdt, Lesca M. 2017. Quantitative trait locus mapping in mice identifies phospholipase Pla2g12a as novel atherosclerosis modifier. In Atherosclerosis, 265, 197-206. doi:10.1016/j.atherosclerosis.2017.08.030. https://pubmed.ncbi.nlm.nih.gov/28917158/