Mgll, also known as monoglyceride lipase, is a key enzyme in lipid metabolism. It regulates metabolism by catabolizing monoacylglycerols (MAGs), including the endocannabinoid 2-arachidonoyl glycerol (2-AG) and some of its bioactive congeners, to the corresponding free fatty acids [2]. It is involved in pathways related to lipid homeostasis and is associated with many biological processes and disease conditions. Gene knockout models of Mgll have been valuable for studying its functions.

In Mgll knockout mice (Mgll-/-), they exhibit elevated tissue levels of MAGs, along with resistance to the metabolic and cardiovascular perturbations induced by a high-fat diet (HFD). This indicates that Mgll is likely to be involved in diet-induced dysmetabolism [2]. Also, in pancreatic cancer, silencing Mgll in PANC-1 cells reduced cell proliferation, migration, and invasion, likely via the P-AKT/AKT pathway, suggesting Mgll promotes pancreatic cancer progression [3]. In endometrial adenocarcinoma, overexpression of Mgll promoted tumor proliferation, metastasis, and progesterone resistance, while knockdown inhibited these processes [1].

In conclusion, Mgll plays essential roles in lipid metabolism and is involved in disease processes such as diet-induced dysmetabolism, pancreatic cancer, and endometrial adenocarcinoma. The use of Mgll knockout mouse models has been crucial in revealing these roles, providing insights into the molecular mechanisms underlying these diseases and potential therapeutic targets.

References:

1. Ma, Xiaohong, Xia, Min, Wei, Lina, Qiu, Chunping, Jiang, Jie. 2022. ABX-1431 inhibits the development of endometrial adenocarcinoma and reverses progesterone resistance by targeting MGLL. In Cell death & disease, 13, 1067. doi:10.1038/s41419-022-05507-z. https://pubmed.ncbi.nlm.nih.gov/36550099/

2. Dione, Niokhor, Lacroix, Sébastien, Taschler, Ulrike, Di Marzo, Vincenzo, Silvestri, Cristoforo. 2020. Mgll Knockout Mouse Resistance to Diet-Induced Dysmetabolism Is Associated with Altered Gut Microbiota. In Cells, 9, . doi:10.3390/cells9122705. https://pubmed.ncbi.nlm.nih.gov/33348740/

3. Li, Weimin, Qian, Jin, Yang, Hanbo, He, Chenghai, Li, Guodong. . MGLL Promotes Pancreatic Cancer Progression and Invasion: Potential Therapeutic Inhibition by Melatonin. In Annals of clinical and laboratory science, 55, 10-18. doi:. https://pubmed.ncbi.nlm.nih.gov/40089287/