Abrogating monoacylglycerol acyltransferase activity in liver improves glucose tolerance and hepatic insulin signaling in obese mice.
Abrogating monoacylglycerol acyltransferase activity in liver improves glucose tolerance and hepatic insulin signaling in obese mice.
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作者：
Hall AM;Soufi N;Chambers KT;Chen Z;Schweitzer GG;McCommis KS;Erion DM;Graham MJ;Su X;Finck BN
单酰基甘油酰基转移酶（MGAT）将单酰基甘油转化为二酰基甘油（DAG），后者是一种通过激活蛋白激酶C（PKC）与肝胰岛素抵抗发生相关的脂质。编码MGAT酶的基因的表达在患有非酒精性脂肪肝病的胰岛素抵抗人类受试者的肝脏中被诱导，但MGAT激活是否是肝脂肪变性或胰岛素抵抗的原因尚不清楚。我们发现，Mogat 1的表达，编码MGAT 1，和MGAT活性也增加饮食诱导肥胖（DIO）和ob/ob小鼠。为了探索MGAT 1在肥胖小鼠肝脏中的代谢作用，我们将针对Mogat 1的反义寡核苷酸（ASO）给予DIO和ob/ob小鼠3周。敲低肝脏中的Mogat 1，降低肝脏MGAT活性，不影响肝脏三酰甘油含量，并意外地增加总DAG含量。Mogat 1抑制也增加了膜和胞质隔室DAG水平。然而，Mogat 1阿索治疗显著改善了肥胖小鼠的葡萄糖耐量和肝脏胰岛素信号传导。总之，肝脏MGAT活性的失活（其在肥胖小鼠中显著增加）改善了葡萄糖耐量和肝脏胰岛素信号传导，而与体重、肝内DAG和TAG含量以及PKC信号传导的变化无关。
Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol (DAG), a lipid that has been linked to the development of hepatic insulin resistance through activation of protein kinase C (PKC). The expression of genes that encode MGAT enzymes is induced in the livers of insulin-resistant human subjects with nonalcoholic fatty liver disease, but whether MGAT activation is causal of hepatic steatosis or insulin resistance is unknown. We show that the expression of Mogat1, which encodes MGAT1, and MGAT activity are also increased in diet-induced obese (DIO) and ob/obmice. To probe the metabolic effects of MGAT1 in the livers of obese mice, we administered antisense oligonucleotides (ASOs) against Mogat1 to DIO and ob/ob mice for 3 weeks. Knockdown of Mogat1 in liver, which reduced hepatic MGAT activity, did not affect hepatic triacylglycerol content and unexpectedly increased total DAG content. Mogat1 inhibition also increased both membrane and cytosolic compartment DAG levels. However, Mogat1 ASO treatment significantly improved glucose tolerance and hepatic insulin signaling in obese mice. In summary, inactivation of hepatic MGAT activity, which is markedly increased in obese mice, improved glucose tolerance and hepatic insulin signaling independent of changes in body weight, intrahepatic DAG and TAG content, and PKC signaling.
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影响因子：
29
作者：
Farese RV Jr;Zechner R;Newgard CB;Walther TC
通讯作者：
Walther TC
DOI：
10.1073/pnas.1203218109
发表时间：
2012-08-21
影响因子：
11.1
作者：
Lee, Yoo Jeong;Ko, Eun Hee;Kim, Jae-Woo
通讯作者：
Kim, Jae-Woo
影响因子：
6.5
作者：
Brown, J. Mark;Betters, Jenna L.;Yu, Liqing
通讯作者：
Yu, Liqing
影响因子：
6.5
作者：
Harris, Lydia-Ann L. S.;Shew, Trevor M.;Wolins, Nathan E.
通讯作者：
Wolins, Nathan E.
DOI：
10.1111/j.0197-3118.2006.05523.x
发表时间：
2006-01-01
期刊：
Journal of the cardiometabolic syndrome
影响因子：
--
作者：
Abdeen, Mohammad Bosem;Chowdhury, Nazif A;Ibdah, Jamal A
通讯作者：
Ibdah, Jamal A