Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis

• Published in: Cell reports (Cambridge) Vol. 43; no. 3; p. 113967
• Main Authors: Carey, Anna, Nguyen, Katie, Kandikonda, Pranathi, Kruglov, Victor, Bradley, Claire, Dahlquist, Korbyn J.V., Cholensky, Stephanie, Swanson, Whitney, Badovinac, Vladimir P., Griffith, Thomas S., Camell, Christina D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2024; Elsevier
• Subjects: Adipose Tissue - metabolism; Animals; CP: Immunology; CP: Metabolism; Inflammation - metabolism; Lipolysis; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Sepsis - metabolism; CP: Immunology; CP: Metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113967

Non-canonical lipolysis induced by inflammatory cytokines or Toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging due to factors including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation; however, the extent to which the non-canonical pathway of lipolysis is active and impacted by immune cells during aging remains unclear. Therefore, we aimed to define the extent to which immune cells from old mice influence non-canonical lipolysis during sepsis. We identified age-associated impairments of non-canonical lipolysis and an accumulation of dysfunctional B1 B cells in the visceral white adipose tissue (vWAT) of old mice. Lifelong deficiency of B cells results in restored non-canonical lipolysis and reductions in pro-inflammatory macrophage populations. Our study suggests that targeting the B cell-macrophage signaling axis may resolve metabolic dysfunction in aged vWAT and attenuate septic severity in older individuals. [Display omitted] •Non-canonical lipolysis induced by sepsis and LPS is impaired in vWAT from old mice•vWAT accumulates B1 B cells with reduced sepsis-induced activation during aging•Old vWAT B1 and B2 B cells have inflammatory transcriptional responses to LPS•Lifelong B cell KO increases non-canonical lipolysis and reduces macrophage inflammation Carey et al. demonstrate that inflammation is increased but lipolysis is reduced following sepsis or endotoxemia in old mice. They identify an accumulation of inflammatory B1 B cells and B2 B cells in the visceral white adipose tissue (vWAT) of old mice. They find that B cells promote pro-inflammatory macrophages and impair non-canonical vWAT lipolysis.