Resveratrol cardioprotection associated with adipose tissue autotaxin pathway inhibition in a diet induced prediabetic female rat model

Abstract

Introduction

Prediabetes is associated with an increased cardiovascular risk, but recent data also highlight the importance of the role of the liver and adipose tissue in cardiovascular risk stratification in this context. These inter-organ relationships still require further investigation, as well as finding new therapeutic approaches, especially in women who present a higher cardiovascular risk than men as early as the prediabetes stage.

Objective

Here, we evaluated the effects of resveratrol supplementation (RSV) on the heart/adipose tissue axis in prediabetic female rats submitted to high-fat-high-sucrose diet (HFS).

Method

30 Female Wistar rats were divided into 3 groups fed for 5 months with: a standard diet (CTRL), HFS diet (HFS) or HFS diet supplemented for the last 2 months with RSV (1 mg/kg/day in water) (RSV). In vivo Magnetic Resonance Imaging was performed to study cardiac morphology/function. Then, tolerance to ischemia-reperfusion (IR) injury was investigated ex vivo by simultaneous measurement of cardiac function (RPP, EDP) and energy metabolism by 31P Magnetic Resonance Spectroscopy. Finally, the expression of autotaxin (ATX) Enpp2 gene, a protein suggested to be involved in deleterious cardiac remodeling, in perirenal adipose tissue as well as its plasma concentration were measured.

Results

HFS diet induced glucose intolerance (P < 0.01 vs CTRL), deleterious cardiac remodeling (P < 0.05 vs CTRL), but also impaired myocardial IR tolerance, with diminished cardiac function (RPP, EDP) along with reduced ATP and PCr percentages of recovery during reperfusion (P < 0.05 vs CTRL). These HFS induced impairments were associated with increased adipose tissue ATX gene relative expression and ATX plasmatic levels (P < 0.05 vs CTRL). RSV supplementation ameliorated glucose intolerance (P < 0.01 vs HFS), restored deleterious cardiac remodeling (P < 0.01 vs HFS) and increased IR tolerance [higher cardiac function and ATP, PCr percentages of recovery during reperfusion (P < 0.01 vs HFS)]. Interestingly, these ameliorations were associated with restored adipose tissue ATX gene expression and plasmatic levels (P < 0.05 vs HFS).

Conclusion

A low dose of resveratrol, administered concurrently to an HFS diet, exerted cardioprotection by deleterious cardiac remodeling inhibition and increased IR tolerance. Interestingly, RSV cardioprotection was associated with the inhibition of autotaxin expression in perirenal adipose tissue and ATX plasmatic levels and suggests a yet unknown action path of RSV.