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Sci Rep. 2018 Oct 12;8(1):15197. doi: 10.1038/s41598-018-33486-9.

NLRP3 Inflammasome Modulates Post-Burn Lipolysis and Hepatic Fat Infiltration via Fatty Acid Synthase.

Author information

1
Sunnybrook Research Institute, Toronto, Canada.
2
Department of Surgery, Division of Plastic Surgery, University of Toronto, Toronto, Canada. marc.jeschke@sunnybrook.ca.
3
Department of Immunology, University of Toronto, Toronto, Canada. marc.jeschke@sunnybrook.ca.
4
Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, Canada. marc.jeschke@sunnybrook.ca.
5
Sunnybrook Research Institute, Toronto, Canada. marc.jeschke@sunnybrook.ca.

Abstract

Burns result in generalized catabolism, lipolysis, and hyperinflammation. NLRP3 inflammasome, a mediator of hyperinflammation, is upregulated in burn patients' adipose tissue within 7 days post-burn. However, its role during the acute phase is unknown. Here, wild-type (WT) and NLRP3 knockout (NLRP3-/-) mice were exposed to 25% TBSA scald burn. Flow cytometric analysis demonstrated greater liver macrophage infiltration in NLRP3-/- yet decreased protein expression of NLRP3 components, ER stress, and apoptosis. NLRP3-/- had increased circulating free fatty acids (FFA), fatty deposition and liver weight 1 hour post-burn. Alterations in adipose fatty acid synthase (Fasn) expression affects FFA levels post-burn; WT have an early peak in Fasn gene and protein expression that is lost in NLRP3-/-, resulting in increased lipolysis and hepatic fatty deposition. In summary, our findings reveal that NLRP3 inflammasome activation is a double-edged sword. While prolonged inflammation and long-term effects of macrophage activation are associated with poor outcomes, acute inflammation may be beneficial. These results highlight the important metabolic role that NLRP3 inflammasome plays in the acute phase, ultimately affecting survival post-burn.

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