Adipocyte-derived inflammatory molecules induce senescent B cells through metabolic pathways.

OBJECTIVE:The aim of this study was to demonstrate that an adipocyte tissue-derived conditioned medium (ACM) contains inflammatory molecules that induce senescence in B cells. METHODS:We incubated blood-derived B cells from lean donors with ACM obtained from the adipose tissue of adult female donors with obesity undergoing weight reduction surgery or with medium as control. After 24 h, cells were harvested, and the expression of transcripts for proinflammatory cytokines (TNF/IL-6), chemokines (IL-8), and for markers of the senescence-associated secretory phenotype (SASP) was measured by quantitative polymerase chain reaction. B cells were also stained with the marker of immunosenescence β-galactosidase, and their metabolic status was evaluated in Seahorse using a Mito Stress Test. RESULTS:We show that the incubation of B cells from lean donors with ACM induces the expression of transcripts for inflammatory and SASP transcripts, increases the amount of β-galactosidase staining, and induces a metabolic phenotype characterized by higher basal and maximal oxygen consumption, spare respiratory capacity (difference between maximal and basal respiration), nonmitochondrial oxygen consumption, ATP production, and proton leak. CONCLUSIONS:These results demonstrate that B cells from lean individuals, after incubation with ACM, become inflammatory and senescent, and this occurs through metabolic pathways needed to support their secretory phenotype.