Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation

Vishal Vyas,Neil Roberts,Carmelo Di Salvo,David Lawrence,Kit Wong,Elizabeth G Wood,John Yap,Rakesh Uppal,Shyam Kolvekar,Alex Shipolini,Damian Balmforth,Shah-Jalal Sarker,M Paula Longhi,Stephen Edmondson ,Aung Oo ,Hazel Blythe ,Malcolm Finlay ,Kulvinder Lall ,Shirish Ambekar ,Balraj Sandhar ,Ben G Adams

doi:10.1172/jci.insight.145495

Abstract

BACKGROUNDEpicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT’s immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients.METHODSWe recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients’ clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups.RESULTSFlow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls.CONCLUSIONAdaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile.FUNDINGBarts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.

Highlights

Epicardial adipose tissue (EAT) is the visceral adipose tissue of the heart, covering 80% of its surface and up to 20% of its weight [1]
The presence of underlying cardiometabolic conditions, obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT
To gain a more complete understanding of the immune profile of EAT, we investigated the presence of key immune populations by flow cytometry

Summary

Introduction

Epicardial adipose tissue (EAT) is the visceral adipose tissue of the heart, covering 80% of its surface and up to 20% of its weight [1]. EAT has been implicated in a host of cardiovascular diseases [2] and has been proposed as a transducer [3] of the effects of systemic conditions such as obesity on the heart. Variable [4, 6, 7], a relationship has been described between EAT size and the severity of coronary artery disease (CAD) [8] as well as cardiovascular events [9, 10]. Epicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients

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