Abstract
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.
Highlights
In a previous study using a rat model of type II diabetes mellitus (DM) rats model, diabetic cardiomyopathy was characterized functionally by the presence of left ventricular (LV) diastolic dysfunction, and histologically by interstitial fibrosis and collagen accumulation [1]
The heart-to-body weight ratios were not significantly different between the Otsuka Long-Evans Tokushima fatty (OLETF)-AL and OLETF-caloric restriction (CR) groups at 40 weeks of age, those were significantly reduced in Long-Evans Tokushima Otsuka (LETO)-CR rats, compared with LETO-AL rats
Systolic blood pressure was significantly lower in OLETF-CR than OLETF-AL rats, but was not significantly different between 8-week-old rats of either strain and 40-week-old LETO rats
Summary
In a previous study using a rat model of type II diabetes mellitus (DM) rats model, diabetic cardiomyopathy was characterized functionally by the presence of left ventricular (LV) diastolic dysfunction, and histologically by interstitial fibrosis and collagen accumulation [1]. Coronary artery diseases are the main cause of heart failure and deteriorating function, the high incidence of diabetic cardiomyopathy indicates that diabetes itself is an important factor in myocardial damage. Conventional therapeutic practices, such as strict control of blood glucose level and avoidance of traditional risk factors, are often effective, but not completely prevent cardiac complications [2]. Several studies conducted on laboratory rodents have shown that CR promotes longevity and ameliorates the age-associated impairment of LV diastolic function, arterial elasticity and heart rate variability [5, 6]
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