title: Inflammation and resolution are associated with upregulation of fatty acid β-oxidation in Zymosan-induced peritonitis.
abstract: Inflammation is a fundamental defensive response to harmful stimuli. However, it can cause damage if it does not subside. To avoid such damage, organisms have developed a mechanism called resolution of inflammation. Here we applied an untargeted metabolomics approach to a sterile and self-resolving animal model of acute inflammation, namely zymosan-induced peritonitis in mice, to examine the effect of inflammation and resolution on the metabolomic profiles. Significant and time-dependent changes in metabolite profiles after zymosan administration were observed in both peritoneal wash fluid (PWF) and plasma. These metabolomic changes correlated well with inflammatory chemokine or cytokine production. In PWF, most of metabolites that could detected increased in zymosan-treated mice, which is suggestive of inflammation, oxidative stress and increased energy demands. In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration. The concentration of the ketone body 3-hydroxybutyric acid (3-HB) in plasma and PWF increased in zymosan-injected animals indicating upregulation of fatty acid β-oxidation. Increased 3-HB level was observed in the cells that infiltrated into the peritoneal cavity and these infiltrated cells might contribute, at least in part, to the production of 3-HB in the peritoneal cavity.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Japan ; Asubio Pharma Co., Limited, Kobe, Japan. fujieda.yusuke.aw@asubio.co.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fujieda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manno
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Nelson
authors.initials: N
authors.lastname: Rhodes
authors.forename: Lining
authors.initials: L
authors.lastname: Guo
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000139:chemically induced* / Q000378:metabolism*; D015054:Zymosan / Q000633:toxicity*
chemical_list: D005227:Fatty Acids; D015054:Zymosan