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

Mol Cell Biochem. 2015 May;403(1-2):1-11. doi: 10.1007/s11010-015-2327-0. Epub 2015 Feb 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy*
  • Beclin-1
  • Blotting, Western
  • Caloric Restriction*
  • Caspase 3 / metabolism
  • Diabetes Mellitus, Experimental / enzymology*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diastole*
  • Echocardiography
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism
  • Heart / physiopathology*
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Myocardium / enzymology
  • Myocardium / pathology
  • Nerve Tissue Proteins / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Inbred OLETF
  • Superoxide Dismutase / metabolism
  • Telomerase / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, rat
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Foxo1 protein, rat
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • Proto-Oncogene Proteins c-akt
  • Telomerase
  • Caspase 3