Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression of fatty acid oxidation-related enzymes in rat liver

Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression of fatty acid oxidation-related enzymes in rat liver
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DOI:
10.1016/j.metabol.2003.07.007
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发表时间:
2003-12-01
影响因子:
9.8
通讯作者:
Tsutsumi, K
Tsutsumi, K
中科院分区:
医学1区
文献类型:
--
作者:
Doi, M;Kondo, Y;Tsutsumi, K

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脂蛋白脂酶(LPL)激活剂NO-1886(ibrobromim)已被证明对治疗大鼠肥胖症具有潜在益处。然而,NO-1886的抗肥胖机制尚未完全清楚。为了解决这个问题,我们研究了NO-1886对大鼠脂肪酸氧化相关酶mRNA表达的影响。在进食和禁食条件下,单次经口给予NO-1886的大鼠的呼吸商(RQ)显著低于对照组大鼠。NO-1886经口给予大鼠7天,引起肉毒碱棕榈酰转移酶系统中肉毒碱棕榈酰转移酶II(CPTII)mRNA增加1.54倍。此外,NO-1886导致大鼠中长链酰基辅酶A脱氢酶(LCAD)mRNA增加1.47倍,乙酰辅酶A酰基转移酶2(ACAA 2)mRNA增加1.49倍,烯酰辅酶A水合酶(ECH)mRNA增加1.24倍,所有这些都是肝脏β-氧化酶。与对照组相比,NO-1886还使肝脏中的解偶联蛋白-2(UCP 2)mRNA水平增加了1.42倍。这些结果表明,LPL激活剂NO-1886可以加速脂肪酸氧化相关酶的表达,导致RQ降低。(C)2003年爱思唯尔公司All rights reserved.
The lipoprotein lipase (LPL) activator NO-1886 (ibrolipim) has been shown to have potential benefits for the treatment of obesity in rats. However, the anti-obesity mechanism of NO-1886 has not been clearly understood. To address this, we studied the effects of NO-1886 on the mRNA expression of fatty acid oxidation-related enzymes in rats. The respiratory quotient (RQ) in rats administered a single oral dose of NO-1886 was significantly lower than control rats under both fed and fasted conditions. NO-1886 orally administered to rats for 7 days caused 1.54-fold increase in carnitine palmitoyl transferase II (CPTII) mRNA in the carnitine palmitoyl transferase system. Furthermore, NO-1886 caused a 1.47-fold increase in long-chain acyl-CoA dehydrogenase (LCAD) mRNA, a 1.49-fold increase in acetyl-CoA acyltransferase 2 (ACAA2) mRNA, and a 1.24-fold increase in enoyl-CoA hydratase (ECH) mRNA in rats, all which are liver beta-oxidation enzymes. NO-1886 also increased uncoupling protein-2 (UCP2) mRNA levels in liver by 1.42-fold when compared to the control group. These results suggest that the LPL activator NO-1886 may accelerate the expression of fatty acid oxidation-related enzymes, resulting in a reduction of RQ. (C) 2003 Elsevier Inc. All rights reserved.