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

Area of Science:

• Cardiovascular Biology
• Adipose Tissue Metabolism
• Endothelial Function

Background:

• Epicardial adipose tissue (EAT) produces adiponectin, an insulin-sensitizing and anti-atherogenic protein crucial for heart health.
• Adiponectin production declines in coronary artery disease, suggesting EAT dysfunction plays a role in disease progression.

Purpose of the Study:

• To investigate how glucose and inflammation regulate adiponectin in EAT and subcutaneous adipose tissue (SAT) stromal cells.
• To determine the paracrine effects of these stromal cells on endothelial cells.

Main Methods:

• Stromal cells from EAT and SAT were cultured and induced to undergo adipogenesis under varying glucose concentrations (117, 200, 295 mg/dl) with or without macrophage-conditioned medium (MCM).
• Adiponectin, GLUT-4, and insulin receptor expression were analyzed using real-time PCR.
• Co-cultures with endothelial cells assessed paracrine effects under high glucose, MCM, and myocardial infarction leukocyte-conditioned medium, measuring vascular adhesion molecule expression.

Main Results:

• EAT stromal cells exhibited a U-shaped glucose dose-response for adiponectin expression, unlike SAT stromal cells.
• Macrophage-conditioned medium reduced adiponectin expression in EAT stromal cells during adipogenesis.
• EAT stromal cells promoted endothelial inflammation, an effect exacerbated by inflammatory cell-conditioned medium from myocardial infarction patients.

Conclusions:

• High glucose and inflammation reduce adiponectin expression in EAT stromal cells, contributing to endothelial inflammation.
• EAT stromal cell dysfunction, particularly under inflammatory conditions, promotes processes that advance coronary atherosclerosis.
• Mature adipocytes, as adiponectin producers, may mitigate these deleterious inflammatory effects.