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

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.

心包脂肪组织既包括心外膜脂肪组织（EAT）和心脏脂肪组织（PAT），最近被认为是心血管疾病病理生理学的新因素，尤其是冠状动脉疾病（CAD）。这项研究的目的是评估人类食品，PAT和皮下脂肪组织（SAT）中棕色特征和蛋白质组的差异，以鉴定引起CAD的候选分子。在心包脂肪组织中高度表达解偶联蛋白1（UCP-1）和其他与棕色相关的蛋白质，但在同一非CAD患者的SAT中弱表达。此外，心包脂肪组织的热发生比SAT显示更高。但是，在CAD心包脂肪中，与棕色相关的基因较低。值得注意的是，在CAD的心包脂肪组织中，参与糖酵解，三羧酸周期和脂肪酸代谢的代谢酶水平较低。饮食是与主动脉根相邻的器官，而没有解剖障碍，与PAT不同。我们发现，核糖体蛋白S3A（RPS3A）的表达在人类食品以及小鼠周围的脂肪组织（PVAT）中降低。 RPS3A的敲低显着抑制前脂肪细胞中的脂肪细胞分化，并损害了成熟脂肪细胞中线粒体的功能。此外，小鼠脂肪组织中的RPS3A敲低PVAT的褐变，加速的血管炎症和动脉粥样硬化进展。从机械上讲，RPS3A可以迁移到线粒体以维持棕色脂肪细胞的功能。这些发现提供了令人信服的证据，表明RPS3A是调节EAT中用于预防CAD的棕色脂肪特异性基因UCP-1和碳代谢酶的关键因素。