Ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease

Ketone bodies , β-hydroxybutyrate (BHB) and acetoacetate support mammalian survival during states of energy deficit by serving as alternative source of ATP1. BHB levels are elevated during starvation, high-intensity exercise or by the low carbohydrate ketogenic diet2. Prolonged caloric Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Address and Correspondence to: Vishwa Deep Dixit, Ph.D, Section of Comparative Medicine and Department of Immunobiology, Yale School of Medicine, 310 Cedar St, New Haven CT06520, [email protected], Phone: 203-785-2525, Fax: 203-785-7499. *Authors contributed equally to this work. Author contributions: Y.H.Y. and K.Y.N . contributed equally to the study, They designed and conducted majority of in vitro and all of in vivo experiments, analyzed and interpreted the data and participated in writing the manuscript. R.W.G. participated in design and conduct of inflammasome activation experiments. ELG performed ASC speck and neutrophil assays. MB and AB performed the human monocytes experiments. DK and TMF synthesized the BHB-nanolipogels and conducted control experiments to determine the dose response. DDA formulated the ketone diester diet. NP conducted the ICP-MS experiments to determine K+ efflux. CL and TDK conducted the F.tularensis and S. typhimurium infections experiments. TH designed the experiments and provided essential reagents for experiments involving mitochondrial ROS and UCP2. PAC generated the macrophage specific Scot deficient mice and contributed in experiment design. SK and EA designed and conducted the ASC oligomerization experiments. VDD conceived and supervised the project, interpreted the data and wrote the manuscript. HHS Public Access Author manuscript Nat Med. Author manuscript; available in PMC 2015 September 01. Published in final edited form as: Nat Med. 2015 March ; 21(3): 263–269. doi:10.1038/nm.3804. A uhor M anscript