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

Area of Science:

• Immunology
• Cell Biology
• Metabolism

Background:

• Obesity is linked to chronic inflammation and altered immune cell function.
• Adipose tissue plays a role in systemic inflammation.
• B cells are implicated in immune responses and can undergo senescence.

Purpose of the Study:

• To investigate if adipocyte tissue-derived conditioned medium (ACM) induces senescence in B cells.
• To identify inflammatory molecules in ACM that trigger B cell senescence.
• To explore the metabolic changes associated with ACM-induced B cell senescence.

Main Methods:

• B cells from lean donors were incubated with ACM from obese donors or control medium.
• Quantitative PCR was used to measure inflammatory and senescence-associated secretory phenotype (SASP) transcripts.
• Beta-galactosidase staining and Seahorse Mito Stress Test assessed immunosenescence and metabolic status.

Main Results:

• ACM induced inflammatory and SASP transcripts in B cells.
• Increased beta-galactosidase staining indicated B cell senescence.
• Metabolic analysis revealed higher oxygen consumption, ATP production, and proton leak.

Conclusions:

• ACM from obese individuals induces inflammatory and senescent phenotypes in lean B cells.
• Metabolic reprogramming is crucial for supporting the secretory phenotype of senescent B cells.
• These findings highlight a mechanism by which adipose tissue in obesity may impair immune function.