Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism
Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism
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DOI：
10.1016/j.cardiores.2005.04.018
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发表时间：
2005-09-01
影响因子：
10.8
通讯作者：
Kitakaze, M
中科院分区：
文献类型：
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作者：
Liao, YL;Takashima, S;Kitakaze, M
目的：胰岛素抵抗（IR）与慢性心力衰竭（CHF）相关。脂联素是一种具有抗炎活性的胰岛素增敏激素，通过amp活化蛋白激酶（AMPK）改善能量代谢。AMPK缺乏与应激条件下心脏功能下降有关。然而，脂联素是否在CHF中起重要作用尚不清楚。我们推测脂联素的缺乏可能导致心力衰竭的恶化。方法：采用脂联素缺失小鼠及其窝代，研究脂联素对左室压力负荷过度引起的心肌肥厚和心力衰竭的影响，并探讨其机制。结果：经主动脉横缩（TAC）后3周，脂联素KO小鼠心肌肥厚（野生型（WT）小鼠为7.62 +/- 0.27，敲除型（KO）小鼠为9.97 +/- 1.13,P < 0.05）和肺充血（肺-体重比：WT小鼠为9.05 +/- 1.49，KO小鼠为14.95 +/- 2.36,P < 0.05）显著高于WT小鼠。KO小鼠的左室尺寸也增加。与WT TAC小鼠相比，KO TAC小鼠AMPKot蛋白表达量较低，IR表达量较高。结论：脂联素缺乏可通过降低AMPK信号和糖代谢受损介导压力过载状态下的进行性心脏重构。(c) 2005年欧洲心脏病学会。Elsevier B.V.版权所有。
Objective: Insulin resistance (IR) was reported to be associated with chronic heart failure (CHF). Adiponectin, an insulin-sensitizing hormone with anti-inflammatory activity, improves energy metabolism via AMP-activated protein kinase (AMPK). AMPK deficiency is associated with depressed cardiac function under stress conditions. However, it is not clear whether adiponectin plays an important role in CHF. We hypothesize that deficiency of adiponectin might result in deterioration of heart failure.Methods: Using adiponectin null mice and their littermates, we examined the effects of adiponectin on LV pressure overload-induced cardiac hypertrophy and failure, and investigated the mechanisms involved.Results: Three weeks after transverse aortic constriction (TAC), cardiac hypertrophy (evaluated from the heart-to-body weight ratio: 7.62 +/- 0.27 in wild-type (WT) mice, 9.97 +/- 1.13 in knockout (KO) mice, P < 0.05) and pulmonary congestion (lung-to-body weight ratio: 9.05 +/- 1.49 in WT mice, 14.95 +/- 2.36 in KO mice, P < 0.05) were significantly greater in adiponectin KO mice than WT mice. LV dimensions were also increased in KO mice. Compared with WT TAC mice, expression of AMPKot protein was lower, while IR was higher in KO TAC mice.Conclusion: These findings indicate that adiponectin deficiency leads to progressive cardiac remodeling in pressure overloaded condition mediated via lowing AMPK signaling and impaired glucose metabolism. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.