Understanding The Role Of Pentraxin 3 In Adipose Tissue Inflammation And Aging

Abstract

Obesity and aging are often accompanied by chronic low-grade inflammation in adipose tissue. Metabolic endotoxemia (elevated circulating lipopolysaccharide [LPS] level) is the inducer of systemic and adipose tissue inflammation and dysfunction, which is developed during obesity and aging. As a soluble pattern recognition receptor, Pentraxin 3 (PTX3) plays a vital role in innate immunity and can be induced by inflammatory stimuli in adipose tissue and adipocyte. Altered PTX3 levels have been observed in adipose tissue and blood during obesity and aging, while the role of PTX3 in adipose tissue during inflammation and aging is not fully understood. My Ph.D. research attempts to understand the role of PTX3 in adipose tissue inflammation and aging. In the first project, we investigated how PTX3 regulates inflammation in adipose tissue, and we found that PTX3 plays an anti-inflammatory role partially by regulating miR-21 expression and secretion in brown adipocytes. In the second project, we explored PTX3 secretion from adipose tissue and adipocyte and found that PTX3 is secreted mainly through conventional protein secretion, while a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes. In the third project, we examined the physiological role of PTX3 in adipose tissue during aging, and we showed that PTX3 deficiency induced senescence and inflammation in adipose tissue and promoted lipid transport and oxidation in white adipose tissue of old female mice. In summary, my doctoral research reveals that adipose-derived PTX3 plays an essential role in regulating LPS-stimulated inflammation and cellular senescence during aging, and adipocyte-derived PTX3 is secreted via conventional protein secretion and exosomes.