Decrease of Cardiac Parkin Protein in Obese Mice.

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

doi:10.3389/fcvm.2019.00191

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.

Highlights

Mitochondrial clearance through mitophagy is a major element of mitochondrial homeostasis and plays an important role in maintaining cardiac well-being at baseline as well as during stress [1]
Its role in the heart has been reevaluated in the light of the fact that Parkin deficiency at baseline did not induce cardiac dysfunction; Parkin is required for cardioprotection by ischemic preconditioning or statin administration [5, 6] and we previously reported that diet-induced obesity increases ischemic injury [7]
Mice fed with a high-fat diet (HFD) exhibit a significant decrease in Parkin protein level (Figures 1A,B)

Summary

Introduction

Mitochondrial clearance through mitophagy is a major element of mitochondrial homeostasis and plays an important role in maintaining cardiac well-being at baseline as well as during stress [1]. Mitophagy occurs through different pathways involving Parkin, BNIP3, or FUNDC1. These appear to be complementary and differentially activated according to the stimulus [2, 3]. Parkin-dependent mitophagy has been well studied in the context of myocardial injury after ischemia/reperfusion (I/R) [4]. Its role in the heart has been reevaluated in the light of the fact that Parkin deficiency at baseline did not induce cardiac dysfunction; Parkin is required for cardioprotection by ischemic preconditioning or statin administration [5, 6] and we previously reported that diet-induced obesity increases ischemic injury [7]. The aim of this study was to examine how Parkin-mediated mitophagy was regulated in a model of diet-induced obesity in mice

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Conclusion