Carboxylesterase 2 (CES2/Ces2) proteins exert established roles in (pro)drug metabolism. Recently, human and murine CES2/Ces2c have been discovered as triglyceride (TG) hydrolases implicated in the development of obesity and fatty liver disease. The murine Ces2 family consists of seven homologous genes as opposed to a single CES2 gene in humans. However, the mechanistic role of Ces2 protein family members is not completely understood. In this study, we examined activities of all Ces2 members towards TGs, diglycerides (DGs) and monoglycerides (MGs) as substrate. Besides CES2/Ces2c, we measured significant TG hydrolytic activities for Ces2a, Ces2b, and Ces2e. Notably, these Ces2 members and CES2 efficiently hydrolyzed DGs and MGs and their activities even surpassed those measured for TG hydrolysis. The localization of CES2/Ces2c proteins at the ER may implicate a role of these lipases in lipid signaling pathways. We found divergent expression of Ces2 genes in the liver and intestine of mice on high fat diet, which could relate to changes in lipid signaling. Finally, we demonstrate reduced CES2 expression in the colon of patients with inflammatory bowel disease and a similar decline in Ces2 expression in the colon of a murine colitis model. Together, these results demonstrate that CES2/Ces2 members are highly efficient DG and MG hydrolases that may play an important role in liver and gut lipid signaling.

中文翻译：

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羧酸酯酶 2 蛋白是有效的甘油二酯和单甘油酯脂肪酶，可能与代谢疾病有关。


羧酸酯酶 2 (CES2/Ces2) 蛋白在（前）药物代谢中发挥既定作用。最近，人类和鼠类 CES2/Ces2c 被发现是甘油三酯 (TG) 水解酶，与肥胖和脂肪肝疾病的发展有关。小鼠 Ces2 家族由七个同源基因组成，而人类只有一个 CES2 基因。然而，Ces2 蛋白家族成员的机制作用尚不完全清楚。在这项研究中，我们检查了所有 Ces2 成员对 TG、甘油二酯 (DG) 和甘油单酯 (MG) 作为底物的活性。除了 CES2/Ces2c 之外，我们还测量了 Ces2a、Ces2b 和 Ces2e 的显着 TG 水解活性。值得注意的是，这些 Ces2 成员和 CES2 有效水解了 DG 和 MG，其活性甚至超过了 TG 水解测量的活性。 CES2/Ces2c 蛋白在内质网的定位可能暗示这些脂肪酶在脂质信号通路中的作用。我们发现高脂饮食小鼠的肝脏和肠道中 Ces2 基因的表达存在差异，这可能与脂质信号传导的变化有关。最后，我们证明了炎症性肠病患者结肠中 CES2 表达的减少以及小鼠结肠炎模型结肠中 Ces2 表达的类似下降。总之，这些结果表明 CES2/Ces2 成员是高效的 DG 和 MG 水解酶，可能在肝脏和肠道脂质信号传导中发挥重要作用。