RPS3A positively regulates the mitochondrial function of human periaortic adipose tissue and is associated with coronary artery diseases

Abstract

Pericardial adipose tissue, which comprises both epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), has recently been recognized as a novel factor in the pathophysiology of cardiovascular diseases, especially coronary artery disease (CAD). The goal of this study was to evaluate differences in the brown-like characteristic and proteome among human EAT, PAT, and subcutaneous adipose tissue (SAT) to identify candidate molecules causing CAD. Uncoupling protein 1 (UCP-1) and other brown-related proteins were highly expressed in pericardial adipose tissue but was weakly expressed in SAT from the same non-CAD patient. Moreover, pericardial adipose tissues displayed a higher thermogenesis than SAT. However, brown-related genes were lower in CAD pericardial fat. Remarkably, there were lower levels of metabolic enzymes involved in glycolysis, tricarboxylic acid cycle, and fatty acid metabolism in pericardial adipose tissues of CAD. EAT is an organ adjacent to aortic root without anatomy barriers, which differs from PAT. We found that the expression of ribosomal protein S3A (RPS3A) was decreased in human EAT as well as in mouse perivascular adipose tissue (PVAT). Knockdown of RPS3A significantly inhibited adipocyte differentiation in preadipocytes and impaired the function of mitochondria in mature adipocytes. Moreover, RPS3A knockdown in mouse periaortic adipose tissue impaired browning of PVAT, accelerated vascular inflammation, and atherosclerosis progression. Mechanistically, RPS3A can migrate to the mitochondria to maintain the function of brown adipocytes. These findings provide compelling evidence that RPS3A was a key factor for modulating the brown fat-specific gene UCP-1 and carbon metabolic enzymes in EAT for preventing CAD.