Abstract
A hallmark after burn is the stress and inflammatory-induced hypermetabolic response. Recently, we and others found that browning of white adipose tissue (WAT) is a critical component of this complex detrimental response. Although browning and inflammation have been independently delineated to occur after injury, their interaction is currently not well defined. One of the master regulators of inflammation and adipose tissue remodeling after burns is nucleotide-binding and oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome. The aim of this this study was to determine whether NLRP3 modulates and activates WAT browning after burn. To obtain molecular and mechanistic insights, we used an NLRP3 knockout (NLRP3-/-) murine burn model. We demonstrated that genetic deletion of NLRP3 promoted persistent and augmented browning in adipocytes, evidenced by increased gene expression of peroxisome proliferator-activated receptor γ and CIDEA at 3 days (5.74 vs. 0.29, P < 0.05; 26.0 vs. 0.71, P < 0.05) and uncoupling protein 1 (UCP1) and PGC1α at 7 days (7,406 vs. 3,894, P < 0.05; 20.6 vs. 2.52, P < 0.01) and enhanced UCP1 staining and multilocularity. Additionally, the main regulator of postburn WAT browning, IL-6, was elevated in the plasma acutely after burn in NLRP3-/- compared with wild-type counterparts (478.9 vs. 67.1 pg/mL, P < 0.05 at 3 days). These results suggest that NLRP3 has antibrowning effects and that blocking NLRP3 increases thermogenesis and augments browning via increased levels of IL-6. Our findings provide insights into targeting innate inflammatory systems for regulation of adaptive thermogenesis, a critical response after burns and other hypermetabolic conditions.
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