Decrease of Cardiac Parkin Protein in Obese Mice

Amandine Thomas; Stefanie Marek-Iannucci; Kyle C Tucker; Allen M Andres; Roberta A Gottlieb

doi:10.3389/fcvm.2019.00191

Decrease of Cardiac Parkin Protein in Obese Mice

Front Cardiovasc Med. 2020 Jan 20:6:191. doi: 10.3389/fcvm.2019.00191. eCollection 2019.

Authors

Amandine Thomas¹, Stefanie Marek-Iannucci¹, Kyle C Tucker¹, Allen M Andres¹, Roberta A Gottlieb¹

Affiliation

¹ Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, United States.

Abstract

Mitophagy plays a major role in heart physiology. Impairment of Parkin-dependent mitophagy in heart is known to be deleterious. Obesity is a known cardiovascular risk factor. Impaired autophagy has been reported in models of obesity or hyperlipidemia/hypercholesterolemia; however less is known regarding obesity and mitophagy. The aim of this study was to evaluate the regulation of Parkin expression in hearts of mice fed a high fat diet. Interestingly, we found a significant decrease in Parkin protein in hearts of HFD mice compared those fed a low-fat diet. This was associated with mitochondrial dysfunction in the context of ischemia/reperfusion (I/R). This downregulation was not associated with a decrease in Parkin mRNA expression. We did not detect any change in the degradation rate of Parkin and only a slight decrease in its translation. The reduction of Parkin protein abundance in HFD hearts remains a mystery and will need further studies. However, Parkin depletion in the setting of obesity may contribute to cardiovascular risk.

Keywords: Parkin; ischemia/reperfusion; mitochondria; mitophagy; myocardium; obesity.