Small mammalian hibernators use metabolic suppression to enhance survival during the winter. Torpor is punctuated by periods of euthermia used to clear metabolic by-products and damaged cell components. The current study was performed to determine if the innate immune system, specifically NLRP and AIM2 inflammasome signaling, may detect and respond to cell stress during hibernation. Nlrp3, Casp1, and Il1b genes were significantly upregulated in brown adipose tissue (BAT) during arousal with respect to the euthermic control, suggesting increased NLRP3 inflammasome priming. NLRP3, IL-18, and gasdermin D protein levels increased during torpor, indicating a lag between inflammasome priming and formation. AIM2 and gasdermin D levels increased in BAT during arousal, as did caspase-1 activity. Thus, non-shivering thermogenesis may generate pro-inflammatory triggers of inflammasome signaling. This study is the first to support a role for inflammasome signaling in sensing cellular perturbations at various points of the torpor-arousal cycle, in metabolically-active BAT, but not white adipose tissue (WAT).

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Developmental and Comparative Immunology
Institute of Biochemistry

Logan, S.M. (Samantha M.), & Storey, K. (2021). Inflammasome signaling could be used to sense and respond to endogenous damage in brown but not white adipose tissue of a hibernating ground squirrel. Developmental and Comparative Immunology, 114. doi:10.1016/j.dci.2020.103819