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The effect of p66Shc on energy expenditure in mice

Previous investigations have shown that the p66Shc protein has a significant effect on life span. While the mechanism underlying the impact that p66Shc has on life span remains to be elucidated, it has been proposed that p66Shc may interact with the IGF‐1/insulin signaling pathway to modulate metabolism, and possibly energy expenditure, under conditions of stress. As a first step in testing this possibility, oxygen consumption and carbon dioxide production were measured in 3‐month‐old male p66Shc knockout (p66Shc−/−) and wild type C57BL/6 mice for 24h at 23oC and for 5h at 12–13oC. Average 24h energy expenditure (EE) at 23oC did not differ (P > 0.10) between the p66Shc−/− and C57BL/6 groups. Dark vs. light phase EE (12h dark: 12h light) was greater in both groups, but did not differ among p66Shc−/− and C57BL/6 mice. Cold‐exposed EE also did not differ between the groups. RQ measured at 23oC was higher in the p66Shc−/− compared to C57BL/6 mice and this difference was most pronounced during the dark cycle. Cold‐exposed RQ was also greater in the p66Shc−/− vs. C57BL/6 mice (p66Shc−/−, 0.85 ± 0.004; C57BL/6, 0.83 ± 0.005). These preliminary data suggest that while EE does not differ in p66Shc−/− vs. C57BL/6 mice, the mix of substrate used for energy metabolism may be influenced by the p66Shc protein. The influence of the p66Shc protein on substrate utilization observed here is consistent with a role for this protein in the IGF‐1/insulin‐dependent intracellular signally pathway. (Supported by NIH PO1 AG025532)