Metabolic responses to water deprivation in C57BL/6J mice using a proton nuclear magnetic resonance-based metabonomics approachElectronic supplementary information (ESI) available: ESI Table S-1 and ESI Fig. S-1-S-6. See DOI: 10.1039/c5ra12650a

Water deprivation can occur in isolated conditions by a natural disaster or under normal living conditions. However, the mechanism underlying response or adaption to water deprivation in mammals is not fully understood. This study was undertaken to unravel this mechanism. Male C57BL/6J mice were treated without or with water deprivation for four time periods ( i.e. , 1, 2, 3, and 4 days) before sacrifice. In four days of trial, no mice with or without drinking water experienced any mortality. Body weight, serum total protein, albumin, and trans-aminase activity were determined at 24 h intervals for 96 h. During dehydration, the mice's body weight decreased consistently. Moreover, a non-biased proton nuclear magnetic resonance ( 1 H NMR)-based metabonomics strategy was performed to evaluate the effects of water deprivation on the responses of systemic hepatic metabolites in male C57BL/6J mice during a 96 h period. Water deprivation stress caused metabolic disturbance and changes in hepatic metabolites that are involved in the metabolisms of carbohydrates, lipids and amino acids. Under water deprivation stress, lactate and 3-hydroxybutylate might be the main energy sources. Increased taurine and branched chain amino acids (BCAAs) might confer tolerance and adaptability to mice under dehydration stress. Moreover, the increased free fatty acids (FFAs) caused by water deprivation probably contributed to counteracting dehydration related osmolality fluctuations. These results also reveal that the metabonomics strategy is a powerful tool to gain insight into the molecular mechanism of cellular response to environmental stresses. 1 H NMR-based metabonomics approach is effective for elucidating underlying mechanisms response or adaption to water deprivation in mammals. Metabolic relevance of differential compounds in response of C57BL/6J mice to water deprivation was discussed.