title: Alternate day calorie restriction improves systemic inflammation in a mouse model of sepsis induced by cecal ligation and puncture.
abstract: BACKGROUND
  Calorie restriction (CR) exerts cytoprotective effects by up-regulating survival factors, such as mammalian target of rapamycin (mTOR), sirtuin, and peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α). These survival factors have well-established roles in attenuating the inflammatory response. However, it is unclear whether CR affects sepsis-related inflammation. The purpose of this study was to determine whether CR affects sepsis-induced inflammation in a cecal ligation and puncture (CLP)-induced mouse model of sepsis.
  
  
  METHODS
  Male C57BL/6N mice underwent alternate day calorie restriction or normal feeding for 8 d before CLP-induced sepsis. After induction of sepsis, liver and lung histopathology and serum levels of cytokines and survival factors were assessed.
  
  
  RESULTS
  Serum cytokine and high mobility group box protein 1 (HMGB1) levels were lower in animals that underwent alternate day calorie restriction compared with normally-fed mice after CLP. Alternate day calorie restriction also increased levels of sirtuin, PGC-1α, and mTOR. While 80% of mice in the CLP group died within 48 h after undergoing CLP, 50% of mice died in the ACR + CLP group (P < 0.05).
  
  
  CONCLUSIONS
  Alternate day calorie restriction decreased mortality in a mouse model of sepsis. In addition to attenuated organ injury, a significant reduction in cytokine and HMGB1 levels was observed. These findings suggest that alternative day calorie restriction may reduce excessive inflammation.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Asai
authors.forename: Taichi
authors.initials: T
authors.lastname: Nishida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood; D050884:HSP72 Heat-Shock Proteins / Q000032:analysis; D007249:Inflammation / Q000517:prevention & control*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018805:Sepsis / Q000150:complications* / Q000378:metabolism; D037761:Sirtuins / Q000032:analysis; D058570:TOR Serine-Threonine Kinases / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; D050884:HSP72 Heat-Shock Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D037761:Sirtuins