Carboxylesterase 2 proteins are efficient diglyceride and monoglyceride lipases possibly implicated in metabolic disease.
Carboxylesterase 2 proteins are efficient diglyceride and monoglyceride lipases possibly implicated in metabolic disease.
复制标题
DOI：
10.1016/j.jlr.2021.100075
复制
发表时间：
2021
影响因子：
6.5
通讯作者：
Haemmerle G
中科院分区：
文献类型：
--
作者：
Chalhoub G;Kolleritsch S;Maresch LK;Taschler U;Pajed L;Tilp A;Eisner H;Rosina P;Kien B;Radner FPW;Schicho R;Oberer M;Schoiswohl G;Haemmerle G
羧酸酯酶2(CES2/CES2)蛋白在药物代谢中发挥重要作用。最近，人和小鼠的CES2/Ces2c被发现是甘油三酯(TG)水解酶，与肥胖和脂肪肝的发生有关。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蛋白家族成员的作用机制还不完全清楚。在这项研究中，我们检测了所有CES2成员对TGS、双甘酯(DGs)和单甘酯(MGs)作为底物的活性。除CES2/Ces2c外，我们还测定了Ces2a、Ces2b和Ces2e的显著TG水解性。值得注意的是，这些CES2成员和CES2有效地水解DGs和MGs，它们的活性甚至超过了TG的水解值。CES2/Ces2c蛋白在内质网的定位可能暗示了这些脂肪酶在脂质信号通路中的作用。我们发现Ces2基因在高脂饮食小鼠的肝脏和肠道中有不同的表达，这可能与脂质信号的变化有关。最后，我们展示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中结肠中CES2表达的类似下降。综上所述，这些结果表明CES2/CES2成员是高效的DG和MG水解酶，可能在肝脏和肠道的脂质信号中发挥重要作用。
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 toward TGs, diglycerides (DGs), and monoglycerides (MGs) as the 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 a 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.
登录
查看更多内容
人类羧酸酯酶2逆转肥胖引起的二酰基甘油的积累和葡萄糖不耐症。
影响因子：
8.8
作者：
Ruby MA;Massart J;Hunerdosse DM;Schönke M;Correia JC;Louie SM;Ruas JL;Näslund E;Nomura DK;Zierath JR
通讯作者：
Zierath JR
影响因子：
9.7
作者：
Kuehl, Anja A.;Erben, Ulrike;Utku, Nalan
通讯作者：
Utku, Nalan
影响因子：
29
作者：
Zechner R;Zimmermann R;Eichmann TO;Kohlwein SD;Haemmerle G;Lass A;Madeo F
通讯作者：
Madeo F
影响因子：
21.1
作者：
Lian J;Nelson R;Lehner R
通讯作者：
Lehner R
影响因子：
4.8
作者：
Taschler, Ulrike;Radner, Franz P. W.;Zimmermann, Robert
通讯作者：
Zimmermann, Robert