Metabolic alterations due to caloric restriction and every other day feeding in normal and growth hormone receptor knockout mice

Mutations causing decreased somatotrophic signaling are known to increase insulin sensitivity and extend life span in mammals. Caloric restriction and every other day (EOD) dietary regimens are associated with similar improvements to insulin signaling and longevity in normal mice; however, these interventions fail to increase insulin sensitivity or life span in growth hormone receptor knockout (GHRKO) mice. To investigate the interactions of the GHRKO mutation with caloric restriction and EOD dietary interventions, we measured changes in the metabolic parameters oxygen consumption (VO₂) and respiratory quotient produced by either long-term caloric restriction or EOD in male GHRKO and normal mice. GHRKO mice had increased VO₂, which was unaltered by diet. In normal mice, EOD diet caused a significant reduction in VO₂ compared with ad libitum (AL) mice during fed and fasted conditions. In normal mice, caloric restriction increased both the range of VO₂ and the difference in minimum VO₂ between fed and fasted states, whereas EOD diet caused a relatively static VO₂ pattern under fed and fasted states. No diet significantly altered the range of VO₂ of GHRKO mice under fed conditions. This provides further evidence that longevity-conferring diets cause major metabolic changes in normal mice, but not in GHRKO mice.