Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT1-PGC1a energy metabolism pathway

Sci Rep. 2023 Feb 4;13(1):2045. doi: 10.1038/s41598-023-27611-6.

Abstract

A large number of data suggest that caloric restriction (CR) has a protective effect on myocardial ischemia/reperfusion injury (I/R) in the elderly. However, the mechanism is still unclear. In this study, we created the I/R model in vivo by ligating the mice left coronary artery for 45 min followed by reperfusion. C57BL/6J wild-type mice were randomly divided into a young group fed ad libitum (y-AL), aged fed ad libitum (a-AL) and aged calorie restriction group (a-CR, 70% diet restriction), and fed for 6 weeks. The area of myocardial infarction was measured by Evan's blue-TTC staining, plasma cholesterol content quantified by ELISA, fatty acids and glucose measured by Langendorff working system, as well as protein expression of AMPK/SIRT1/PGC1a signaling pathway related factors in myocardial tissue detected by immunoblotting. Our results showed that CR significantly reduced infarct size in elderly mice after I/R injury, promoted glycolysis regardless of I/R injury, and restored myocardial glucose uptake in elderly mice. Compared with a-AL group, CR significantly promoted the expression of p-AMPK, SIRT1, p-PGC1a, and SOD2, but decreased PPARγ expression in aged mice. In conclusion, our results suggest that CR protects elderly mice from I/R injury by altering myocardial substrate energy metabolism via the AMPK/SIRT1/PGC1a pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Caloric Restriction
  • Energy Metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Reperfusion Injury*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Substances

  • AMP-Activated Protein Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sirt1 protein, mouse
  • Ppargc1a protein, mouse