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

Makino N, Oyama J, Maeda T, Koyanagi M, Higuchi Y, Tsuchida K - Mol. Cell. Biochem. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan, makino0108@gmail.com.

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.

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Protein expression of p-Akt, p-FoxO1, and p-FoxO3 in the hearts of LETO and OLETF rats with or without CR. a Representative results. b Summarized results. Open bar indicates rats fed ad libitum (AL) and closed bar indicates rats with calorie restriction (CR) in each strain. Each group contained 6 animals. Values are the mean ± SE. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats
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Fig1: Protein expression of p-Akt, p-FoxO1, and p-FoxO3 in the hearts of LETO and OLETF rats with or without CR. a Representative results. b Summarized results. Open bar indicates rats fed ad libitum (AL) and closed bar indicates rats with calorie restriction (CR) in each strain. Each group contained 6 animals. Values are the mean ± SE. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats

Mentions: We also investigated the cell signaling for CR in the LETO and OLETF rats fed an AL or a CR diet (Fig. 1). The protein levels for p-Akt were lower in the OLETF-AL than in either the LETO-AL and LETO-CR rats. These reductions in expression were induced to enhance both of phospho-FoxO1 and phospho-FoxO3 in OLETF-AL rats, while those expressions were reduced in OLETF-CR rats. To further examine the antioxidant enzyme, manganese superoxide dismutase (MnSOD), cleaved caspase-3, indicators of cellular apoptosis, and endothelial nitric oxide synthase (eNOS) were also assessed by Western blot analysis (Fig. 2a). In OLETF-AL rats, the protein expressions of MnSOD and eNOS were significantly attenuated and those of cleaved caspase-3 were significantly enhanced. However, these changes were not observed in OLETF-CR rats (Fig. 2b). The DNA fragmentation in the hearts was also examined (Fig. 2c). The lane 4 from OLETF-AL rats indicated the enhanced fragmentations, but those of OLETF-CR (lane 5) did not (Fig. 2d). These results indicate that CR has beneficial effects for reduction of oxidant stress which was the increases of antioxidant enzymes and the inhibition of apoptosis in myocardium of OLETF rats.Fig. 1


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

Makino N, Oyama J, Maeda T, Koyanagi M, Higuchi Y, Tsuchida K - Mol. Cell. Biochem. (2015)

Protein expression of p-Akt, p-FoxO1, and p-FoxO3 in the hearts of LETO and OLETF rats with or without CR. a Representative results. b Summarized results. Open bar indicates rats fed ad libitum (AL) and closed bar indicates rats with calorie restriction (CR) in each strain. Each group contained 6 animals. Values are the mean ± SE. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383823&req=5

Fig1: Protein expression of p-Akt, p-FoxO1, and p-FoxO3 in the hearts of LETO and OLETF rats with or without CR. a Representative results. b Summarized results. Open bar indicates rats fed ad libitum (AL) and closed bar indicates rats with calorie restriction (CR) in each strain. Each group contained 6 animals. Values are the mean ± SE. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats
Mentions: We also investigated the cell signaling for CR in the LETO and OLETF rats fed an AL or a CR diet (Fig. 1). The protein levels for p-Akt were lower in the OLETF-AL than in either the LETO-AL and LETO-CR rats. These reductions in expression were induced to enhance both of phospho-FoxO1 and phospho-FoxO3 in OLETF-AL rats, while those expressions were reduced in OLETF-CR rats. To further examine the antioxidant enzyme, manganese superoxide dismutase (MnSOD), cleaved caspase-3, indicators of cellular apoptosis, and endothelial nitric oxide synthase (eNOS) were also assessed by Western blot analysis (Fig. 2a). In OLETF-AL rats, the protein expressions of MnSOD and eNOS were significantly attenuated and those of cleaved caspase-3 were significantly enhanced. However, these changes were not observed in OLETF-CR rats (Fig. 2b). The DNA fragmentation in the hearts was also examined (Fig. 2c). The lane 4 from OLETF-AL rats indicated the enhanced fragmentations, but those of OLETF-CR (lane 5) did not (Fig. 2d). These results indicate that CR has beneficial effects for reduction of oxidant stress which was the increases of antioxidant enzymes and the inhibition of apoptosis in myocardium of OLETF rats.Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan, makino0108@gmail.com.

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.

Show MeSH
Related in: MedlinePlus