Aging induces Nlrp3 inflammasome dependent adipose B cell expansion to impair metabolic homeostasis

Summary

Visceral adiposity in elderly is associated with alterations in adipose tissue immune cells leading to inflammation and metabolic dysfunction. The Nlrp3 inflammasome is a critical regulator of macrophage activation, inflammation, and immunometabolism in visceral adipose tissue during aging; however, the potential contribution of adipose tissue B cells is unexplored. Here, we show that aging expands adipose-resident B cells and fat-associated lymphoid clusters (FALCs) in visceral white adipose tissue. Adipose tissue B cells exhibit a memory-like B cell profile similar to the phenotype of aged B cells that are increased in spleen of old mice. Mechanistically, the age-induced FALC formation and adipose B cell expansion, but not B cell transcriptional program, is dependent on the Nlrp3 inflammasome. Furthermore, B cell depletion in aged mice restores lipolysis and defense against loss of core body temperature during cold stress. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging adipose tissue.

Highlights

- Adipose-resident aged B cells are increased in fat-associated lymphoid clusters (FALC)

- FALC formation and adipose-resident B cell expansion during aging are regulated by the Nlrp3 inflammasome

- Nlrp3 and B cell depletion in aging restores lipolysis and improves cold tolerancea