Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis

Christina D. Camell, Patrick Günther, Aileen Lee, Emily L. Goldberg, Olga Spadaro, Yun Hee Youm, Andrzej Bartke, Gene B. Hubbard, Yuji Ikeno, Nancy H. Ruddle, Joachim Schultze, Vishwa Deep Dixit

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

During aging, visceral adiposity is often associated with alterations in adipose tissue (AT) leukocytes, inflammation, and metabolic dysfunction. However, the contribution of AT B cells in immunometabolism during aging is unexplored. Here, we show that aging is associated with an expansion of a unique population of resident non-senescent aged adipose B cells (AABs) found in fat-associated lymphoid clusters (FALCs). AABs are transcriptionally distinct from splenic age-associated B cells (ABCs) and show greater expansion in female mice. Functionally, whole-body B cell depletion restores proper lipolysis and core body temperature maintenance during cold stress. Mechanistically, the age-induced FALC formation, AAB, and splenic ABC expansion is dependent on the Nlrp3 inflammasome. Furthermore, AABs express IL-1R, and inhibition of IL-1 signaling reduces their proliferation and increases lipolysis in aging. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging AT.

Original languageEnglish (US)
Pages (from-to)1024-1039.e6
JournalCell Metabolism
Volume30
Issue number6
DOIs
StatePublished - Dec 3 2019

Keywords

  • B cell depletion
  • IL-1 signaling
  • Nlrp3 inflammasome
  • adipose tissue B cells
  • age-associated B cells
  • aging
  • fat-associated lymphoid cluster
  • growth hormone receptor
  • inflammaging
  • lipolysis

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  • Cite this

    Camell, C. D., Günther, P., Lee, A., Goldberg, E. L., Spadaro, O., Youm, Y. H., Bartke, A., Hubbard, G. B., Ikeno, Y., Ruddle, N. H., Schultze, J., & Dixit, V. D. (2019). Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis. Cell Metabolism, 30(6), 1024-1039.e6. https://doi.org/10.1016/j.cmet.2019.10.006