Glucose and Inflammatory Cells Decrease Adiponectin in Epicardial Adipose Tissue Cells: Paracrine Consequences on Vascular Endothelium

Abstract

Epicardial adipose tissue (EAT) is a source of energy for heart that expresses the insulin-sensitizer, anti-inflammatory and anti-atherogenic protein, adiponectin. But, in coronary artery disease, adiponectin production declines. Our objective was to determine its regulation by glucose and inflammation in stromal cells from EAT and subcutaneous adipose tissue (SAT) and its paracrine effect on endothelial cells. Stromal cells of EAT and SAT were obtained from patients who underwent cardiac surgery. Adipogenesis was induced at 117, 200, or 295 mg/dl glucose, with or without macrophage-conditioned medium (MCM). Expression of adiponectin, GLUT-4 and the insulin receptor was analyzed by real-time PCR. The paracrine effect of stromal cells was determined in co-cultures with endothelial cells, by exposing them to high glucose and/or MCM, and, additionally, to leukocyte-conditioned medium from patients with myocardial infarction. The endothelial response was determined by analyzing vascular adhesion molecule expression. Our results showed a U-shaped dose-response curve of glucose on adiponectin in EAT, but not in SAT stromal cells. Conversely, MCM reduced the adipogenesis-induced adiponectin expression of EAT stromal cells. The presence of EAT stromal increased the inflammatory molecules of endothelial cells. This deleterious effect was emphasized in the presence of inflammatory cell-conditioned medium from patients with myocardial infarction. Thus, high glucose and inflammatory cells reduced adipogenesis-induced adiponectin expression of EAT stromal cells, which induced an inflammatory paracrine process in endothelial cells. This inflammatory effect was lower in presence of mature adipocytes, producers of adiponectin. These results contribute to understanding the role of EAT dysfunction on coronary atherosclerosis progression.

Omentin treatment of epicardial fat improves its anti‐inflammatory activity and paracrine benefit on smooth muscle cells

“…Omentin activates the kinase AKT , and this pathway might be involved in this process . Because EAT from CAD patients has a low adipogenesis ability and low adiponectin expression levels , omentin treatment might improve the anti‐inflammatory response against proatherogenic factors and reduce the atherogenesis progression . Many authors have described the anti‐inflammatory action of omentin through TNF‐α inhibition in endothelial cells and macrophages .…”

“…In the presence of CAD, omentin may counteract the harm caused by EAT, which is a high producer of proinflammatory cytokines . Nevertheless, there were no data regarding omentin treatment on EAT and its paracrine effect on smooth muscle or endothelial cells.…”

“…HUVECs were isolated as described with some modifications. Sixty thousand HUVECs were seeded per well in 24‐well plates and stimulated with CM of EAT‐SC after 100 ng/mL omentin treatment (CTRL‐SC‐CM, OME‐SC‐CM).…”

“…The differential expression between treated and control samples was represented as the fold change using the 2 ‐ΔΔCt algorithm. Vascular cell adhesion molecule 1 (VCAM‐1) and intercellular molecular adhesion molecular 1 (ICAM‐1) expression levels were determined as previously described .…”

Investigating interactions between epicardial adipose tissue and cardiac myocytes: what can we learn from different approaches?

“…It is unclear what provokes changes in the secretome of EAT to tip the balance between the release of deleterious or beneficial signals. However Fernandez‐Trasancos et al () showed in vitro that inflammatory conditions, and glucose levels, affected adiponectin expression in EAT. The reported effects of a number of adipokines are summarized in Table .…”