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. It is associated with lipid-related metabolic pathways and is of great biological importance in maintaining lipid homeostasis [1,2,3]. Genetic models, such as gene knockout mice, have been valuable in studying Mgll.

Mgll knockout mice (Mgll-/-) exhibit elevated tissue levels of MAGs and resistance to the metabolic and cardiovascular perturbations induced by a high-fat diet (HFD). They show decreased adiposity, improved insulin sensitivity, and altered circulating incretin/adipokine levels in response to HFD. The gut microbiome of Mgll-/-mice is also altered, with different abundances of certain bacteria families compared to wild-type mice, which may contribute to their obesity-resistant phenotype [3]. In endometrial adenocarcinoma, knockdown of Mgll inhibits tumor proliferation, metastasis, and reverses progesterone resistance, while overexpression promotes these processes [4]. In pancreatic cancer, silencing Mgll in PANC-1 cells reduces cell proliferation, migration, and invasion, likely via the P-AKT/AKT pathway [5].

In conclusion, Mgll plays a crucial role in lipid metabolism and is involved in various disease conditions. Studies using Mgll knockout mouse models have revealed its significance in diet-induced dysmetabolism, as well as in the development and progression of certain cancers such as endometrial adenocarcinoma and pancreatic cancer. These findings highlight Mgll as a potential therapeutic target for treating related diseases.