Alternate Day Calorie Restriction Improves Systemic Inflammation in a Mouse Model of Sepsis Induced by Cecal Ligation and Puncture

Background. Calorie restriction (CR) exerts cyto-protective effects by up-regulating survival factors, such as mammalian target of rapamycin (mTOR), sirtuin, and peroxisome proliferator-activated receptor-g co-activator 1 alpha (PGC-1 alpha). 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-1a, and mTOR. While 80% of mice in the CLP group died within 48 h after undergoing CLP, 50% of mice died in the ACR D 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. (C) 2012 Published by Elsevier Inc.