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.
Highlights
Obesity is one of the main causes of metabolic syndrome, and is associated with chronic inflammation and cardiovascular disease[1]
There is accumulating evidence demonstrating that brown adipose tissue (BAT), which is present in areas close to the clavicular, periaortic, cervical, and suprarenal regions, is activated in response to cold exposure[4,6]
Recent studies have shown that perivascular adipose tissue (PVAT), similar to BAT, is a heat-generating organ that is critical for the maintenance of intravascular temperature and vascular homeostasis[7]
Summary
Obesity is one of the main causes of metabolic syndrome, and is associated with chronic inflammation and cardiovascular disease[1]. According to the Framingham Heart Study, metabolic risk factors are more associated with omental adipose tissue than with subcutaneous adipose tissue (SAT)[2] These differences are plausibly due to differences in adipose tissue distribution and metabolism. Positron emission tomography (PET) and X-ray computed tomography (CT) showed that active uncoupling protein 1 (UCP1)-expressing adipocytes, including brown adipocytes or beige cells, are localized close to the clavicular, periaortic, cervical, and suprarenal regions in adulthood[5,6]. Both brown and beige adipocytes are functionally thermogenic and are considered to be promising new therapeutic avenue to combat atherosclerosis and obesity
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