Alternate day calorie restriction improves systemic inflammation in a mouse model of sepsis induced by cecal ligation and puncture

J Surg Res. 2012 May 1;174(1):136-41. doi: 10.1016/j.jss.2010.11.883. Epub 2010 Dec 9.


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).

Conclusion: 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.

MeSH terms

  • Animals
  • Body Weight
  • Caloric Restriction*
  • Cecum / surgery
  • Cytokines / blood
  • Disease Models, Animal
  • HMGB1 Protein / blood
  • HSP72 Heat-Shock Proteins / analysis
  • Inflammation / prevention & control*
  • Ligation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sepsis / complications*
  • Sepsis / metabolism
  • Sirtuins / analysis
  • TOR Serine-Threonine Kinases / analysis
  • Trans-Activators / analysis
  • Transcription Factors


  • Cytokines
  • HMGB1 Protein
  • HSP72 Heat-Shock Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Trans-Activators
  • Transcription Factors
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • Sirtuins