B Cells with a Senescent-Associated Secretory Phenotype Accumulate in the Adipose Tissue of Individuals with Obesity

Daniela Frasca,Maria Romero,Bonnie B Blomberg,Alain Diaz,Denisse Garcia,Seth Thaller

doi:10.3390/ijms22041839

Abstract

Senescent cells accumulate in the adipose tissue (AT) of individuals with obesity and secrete multiple factors that constitute the senescence-associated secretory phenotype (SASP). This paper aimed at the identification of B cells with a SASP phenotype in the AT, as compared to the peripheral blood, of individuals with obesity. Our results show increased expression of SASP markers in AT versus blood B cells, a phenotype associated with a hyper-metabolic profile necessary to support the increased immune activation of AT-derived B cells as compared to blood-derived B cells. This hyper-metabolic profile is needed for the secretion of the pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) that fuel local and systemic inflammation.

Highlights

We have shown that unstimulated B cells from the peripheral blood of individuals with obesity, as compared to those from lean individuals, express higher levels of RNA and protein for multiple inflammaging-associated pro-inflammatory cytokines (e.g., TNF-α)
B cells were isolated from the peripheral blood of individuals with obesity using magnetic beads and from the adipose tissue (AT) of obese surgery patients using flow cytometry and cell sorting
Results show increased expression of several senescence-associated secretory phenotype (SASP) markers in B cells from the blood of obese versus lean individuals, confirming and extending our previously published findings [18]. These SASP markers are expressed at higher levels in B cells from the AT as compared to those from the peripheral blood, providing the first evidence of the presence of senescent B cells in the human AT

Summary

Introduction

B.B. B Cells with a Cellular senescence indicates the irreversible arrest of cell proliferation that is induced by different stress-derived signals. B Cells with a Cellular senescence indicates the irreversible arrest of cell proliferation that is induced by different stress-derived signals It is mediated by the inhibition of cell cycle progression through p16INK4 and/or the activation of cell cycle arrest through p53/p21. Senescent cells accumulate in the body during aging, promote tissue degeneration and malignant transformation, and lead to the development of inflammatory-based age-associated diseases [5,6]. Senescent cells accumulate in the adipose tissue (AT) of mice and humans, and secrete multiple SASP factors that have been shown to induce cell death, increased local and systemic inflammation and recruitment of immune cells, leading to AT dysfunction, insulin resistance and type-2 diabetes [7,8,9]

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