title: Changes of hepatic lipid mediators associated with intake of high-fat diet for 12 weeks in endotoxemic rats using LC-ESI-MS/MS.
abstract: OBJECTIVE
  It has recently been reported that anti-inflammatory lipid mediators are increased in the late phase of acute inflammation, whereas proinflammatory lipid mediators are regulated at the initiation of inflammation. The purpose of this study was to evaluate changes of hepatic lipid mediators due to high-fat diet (HFD) feeding in endotoxemic rats.
  
  
  METHODS
  Male Wistar rats were fed either HFD or control diet for 12 weeks, and were then killed 0, 1.5, and 6 h after lipopolysaccharide (LPS) injection. Analyses included lipidomics assessment of mediators using liquid chromatography-electrospray ionization/multi-stage mass spectrometry; measuring expression of hepatic polyunsaturated fatty acid (PUFA)-oxidizing enzyme, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and inducible nitric oxide synthase mRNA levels; blood biochemical tests; and liver histology.
  
  
  RESULTS
  HFD feeding worsened liver injury, increased expression of TNF-α and IL-6 mRNA, and increased oxidative stress after LPS injection. PUFA-oxidizing enzymes were higher in HFD-fed rats after LPS injection. The proinflammatory prostaglandin (PG)E2 and thromboxane B2 were increased 1.5 h after LPS injection, and had decreased by 6 h in HFD-fed rats. In contrast, potent pro-resolving resolvins derived from eicosapentaenoic acid and docosahexaenoic acid were not detected, but anti-inflammatory epoxyeicosatrienoic acids, lipoxin A4, and 15-deoxy-PGJ2 were increased after LPS injection in HFD-fed rats.
  
  
  CONCLUSIONS
  HFD feeding for 12 weeks enhanced proinflammatory lipid mediators 1.5 h after LPS injection suggesting relation to liver injury.
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nishiokada
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyoshi
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Aoyama-Ishikawa
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Maeshige
authors.affiliation: Department of Nutrition, Kobe University Hospital, Kobe University School of Medicine, Kobe, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Therapeutic Nutrition, Institute of Health Bioscience, Tokushima Graduate School, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Clinical Laboratory, Osaka University Dental Hospital, Osaka, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Usami
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Honda
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan; Department of Nutrition, Kobe University Hospital, Kobe University School of Medicine, Kobe, Japan. Electronic address: musa@kobe-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Usami
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D000072470:Cytochrome P450 Family 4; D059305:Diet, High-Fat; D015536:Down-Regulation; D019446:Endotoxemia / Q000188:drug therapy* / Q000473:pathology; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C465387:Cyp4a1protein, rat; D005231:Fatty Acids, Unsaturated; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C082161:lipopolysaccharide A; D003577:Cytochrome P-450 Enzyme System; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D000072470:Cytochrome P450 Family 4; D039181:Steroid 16-alpha-Hydroxylase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004851:Epoxide Hydrolases
keywords: High-fat diet; Lard; Lipid mediator; Lipidomics; Lipopolysaccharide; Sepsis