Physical Exercise Potentially Targets Epicardial Adipose Tissue to Reduce Cardiovascular Disease Risk in Patients with Metabolic Diseases: Oxidative Stress and Inflammation Emerge as Major Therapeutic Targets.

Thembeka A Nyawo,Phiwayinkosi V Dludla,Carmen Pheiffer,Tawanda M Nyambuya,Sithandiwe E Mazibuko-Mbeje,Bongani B Nkambule,Hans Strijdom,Hanél Sadie-Van Gijsen,Sinenhlanhla X H Mthembu,Luca Tiano

doi:10.3390/antiox10111758

Abstract

Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.

Highlights

These findings suggest that increased epicardial fat thickness (EFT) may not consistently indicate increased cardiovascular diseases (CVDs) risk, especially in older patients with metabolic disease and preserved ejection fraction heart failure
Other studies mentioned in this review show that derangements in the molecular signature of epicardial adipose tissue (EAT) during metabolic disease are related to abnormalities in cardiac mitochondrial functional capacity, as well as myocardial structural and functional competencies that may accelerate CVD risk (Tables 2 and 3)
Increasing research has been directed to identifying the precise pathophysiological mechanisms that are implicated in the development of diverse metabolic complications, including gestational diabetes, an important feature predominantly seen in pregnant patients with type 2 diabetes (T2D) [82,83]

Summary

Introduction

In 2015, Rabkin and Campbell [10] conducted a systematic review and meta-analysis comparing interventions such as exercise, diet or bariatric surgery for their role in reducing EFT to lower CVD risk. More review articles published in 2020 [12] and early 2021 [13,14] have supported the notion that exercise, together with a restricted diet, bariatric surgery and some pharmaceutical interventions, can reduce EAT volume to improve cardiac function These reviews have further highlighted the impact of physical exercise on reducing EFT to attenuate pathological mechanisms, such as those involving inflammation, to improve cardiac function within a setting of metabolic disease. Beyond giving a general overview on increased EAT mass and volume and its impact on CVDs, the current review brings a unique perspective on oxidative stress and inflammation as major pathological consequences that link increased EAT mass and volume to accelerated CVD risk in conditions of metabolic disease

General Overview of EFT and Its Impact on CVDs

Main Findings

New Zealand white rabbits fed HFD for 12 weeks

Evidence on the Impact of Physical Exercise on EFT and CVD-Related Markers

Findings

Summary and Conclusions