Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts.

Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts.
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DOI:
10.1007/s11010-015-2327-0
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发表时间:
2015-05
影响因子:
4.3
通讯作者:
Tsuchida, Keiko
Tsuchida, Keiko
中科院分区:
生物学3区
文献类型:
--
作者:
Makino, Naoki;Oyama, Jun-ichi;Maeda, Toyoki;Koyanagi, Masamichi;Higuchi, Yoshihiro;Tsuchida, Keiko

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本研究的目的是在糖尿病动物模型中研究热量限制(CR)对心脏端粒生物学的影响,并检查参与细胞衰老和心脏功能的信号转导。将 8 周大的雄性 Otsuka Long-Evans Tokushima 脂肪 (OLETF) 糖尿病大鼠分为两组:随意喂养组 (OLETF-AL) 和 CR 喂养组(OLETF-CR:能量减少 30%)。 Long-Evans Tokushima Otsuka (LETO) 非糖尿病大鼠用作对照。 LETO大鼠也分为两组:CR组(LETO-CR)和喂AL组(LETO-AL)。 40周龄时,OLETF-CR大鼠的体重下降了9.7%,胰岛素抵抗也减轻。 OLETF-CR大鼠端粒酶活性显着升高,且端粒酶逆转录酶在这些大鼠中表达更高。然而,每个品系的 AL 和 CR 治疗大鼠的端粒长度 (TL) 没有差异。与 OLETF-CR 大鼠相比,OLETF-AL 大鼠中 FoxO1 和 FoxO3 的蛋白表达增加,但磷酸化 (p)-Akt 水平降低。自噬 LC3II 信号显示 OLETF-CR 大鼠显着增加。超声心动图显示 OLETF-CR 改善了左心室舒张功能障碍,但左心室尺寸没有变化。这项研究表明,CR 可以增加心脏端粒酶活性,而不会导致 TL 损耗,并显着改善舒张功能障碍。这些发现表明心脏端粒酶活性可能在维持正常心脏功能中发挥重要作用。
The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac telomere biology in an animal model of diabetes and to examine the signal transduction involved in cell senescence as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into two groups: a group fed ad libitum (OLETF-AL) and a group fed with CR (OLETF-CR: 30 % energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were also divided into two groups: a CR (LETO-CR) group and a group fed AL (LETO-AL). At 40 weeks of age, the body weight was decreased by 9.7 % and the insulin resistance was less in OLETF-CR rats. Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats. However, the telomere length (TL) was not different between AL- and CR-treated rats of each strain. The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats. Autophagic LC3II signals revealed significant increases in OLETF-CR rats. Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension. This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction. These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.
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