In Vitro Treatment with Metformin Significantly Reduces Senescent B Cells Present in the Adipose Tissue of People with Obesity

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Our previous work has shown that senescent B cells accumulate in the human adipose tissue (AT) of people with obesity, where they express transcripts for markers associated with the senescence-associated secretory phenotype (SASP) and secrete multiple inflammatory mediators. These functions of AT-derived B cells are metabolically supported. Objectives To show that Metformin (MET), a widely used hypoglycemic and antidiabetic drug, is able at least in vitro to decrease frequencies, secretory profile, and metabolic requirements of senescent B cells isolated from the AT of people with obesity. Methods We recruited adult females with obesity (n = 8, age 40 ± 2 y, BMI range: 33-42) undergoing breast reduction surgery, who donated their discarded subcutaneous AT. B cells from stromal vascular fractions isolated after collagenase digestion of the AT were evaluated after in vitro incubation with MET (1 mM × 10 6 B cells) or with a control medium without MET for the following measures: expression of transcripts for SASP-associated markers (p16 INK4a and p21 CIP1/WAF1 ) measured by quantitative polymerase chain reaction (qPCR); secretion of inflammatory cytokines (TNF-α, IL-6, IFN-γ and IL-17A) measured by a Cytometric Bead Array); metabolic characteristics as identified by a glycolytic test and Seahorse technology, and by the expression of transcripts for glucose transporters

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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