Plin5 deficiency exacerbates pressure overload-induced cardiac hypertrophy and heart failure by enhancing myocardial fatty acid oxidation and oxidative stress

Free Radic Biol Med. 2019 Sep:141:372-382. doi: 10.1016/j.freeradbiomed.2019.07.006. Epub 2019 Jul 7.

Abstract

While cardiac hypertrophy and heart failure are accompanied by significant alterations in energy metabolism, more than 50-70% of energy is obtained from fatty acid β-oxidation (FAO) in adult hearts under physiological conditions. Plin5 is involved in the metabolism of lipid droplets (LDs) and is highly abundant in oxidative tissues including heart, liver and skeletal muscle. Plin5 protects the storage of triglyceride (TG) in LDs by inhibiting lipolysis, thereby suppressing excess FAO and preventing excessive oxidative stress in the heart. In this study, we investigated the roles of Plin5 in cardiac hypertrophy and heart failure in mice treated with transverse aortic constriction (TAC). The results indicated that Plin5 deficiency aggravated myocardial hypertrophy in the TAC-treated mice and exacerbated the TAC-induced heart failure. We also found that Plin5 deficiency reduced the cardiac lipid accumulation and upregulated the levels of PPARα and PGC-1α, which stimulate mitochondrial proliferation. Moreover, Plin5 deficiency aggravated the TAC-induced oxidative stress. We consistently found that Plin5 knockdown disrupted TG storage and elevated FAO and lipolysis in H9C2 rat cardiomyocytes. In addition, Plin5 knockdown also provoked mitochondrial proliferation and lipotoxic injury in H9C2 cells. In conclusion, Plin5 deficiency increases myocardial lipolysis, elevates FAO and oxidative burden, and thereby exacerbates cardiac hypertrophy and heart failure in TAC-treated mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / genetics*
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Energy Metabolism / genetics
  • Fatty Acids / genetics
  • Fatty Acids / metabolism
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Humans
  • Lipid Droplets / metabolism
  • Lipid Metabolism / genetics
  • Lipid Peroxidation / genetics
  • Mice
  • Myocardial Contraction / genetics
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / genetics
  • Perilipin-5 / deficiency
  • Perilipin-5 / genetics*
  • Pressure / adverse effects
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • Perilipin-5
  • Triglycerides