The Influence of Shc Proteins and Aging on Whole Body Energy Expenditure and Substrate Utilization in Mice

Abstract

While it has been proposed that Shc family of adaptor proteins may influence aging by regulating insulin signaling and energy metabolism, the overall impact of Shc proteins on whole body energy metabolism has yet to be elucidated. Thus, the purpose of this study was to determine the influence of Shc proteins and aging on whole body energy metabolism in a mouse model under ambient conditions (22°C) and acute cold exposure (12°C for 24 hours). Using indirect respiration calorimetry, we investigated the impact of Shc proteins and aging on EE and substrate utilization (RQ) in p66 Shc−/− (ShcKO) and wild-type (WT) mice. Calorimetry measurements were completed in 3, 15, and 27 mo mice at 22°C and 12°C. At both temperatures and when analyzed across all age groups, ShcKO mice demonstrated lower 24 h total EE values than that of WT mice when EE data was expressed as either kJ per mouse, or adjusted by body weight or crude organ mass (ORGAN) (P≤0.01 for all). The ShcKO mice also had higher (P<0.05) fed state RQ values than WT animals at 22°C, consistent with an increase in glucose utilization. However, Shc proteins did not influence age-related changes in energy expenditure or RQ. Age had a significant impact on EE at 22°C, regardless of how EE data was expressed (P<0.05), demonstrating a pattern of increase in EE from age 3 to 15 mo, followed by a decrease in EE at 27 mo. These results indicate a decline in whole body EE with advanced age in mice, independent of changes in body weight (BW) or fat free mass (FFM). The results of this study indicate that both Shc proteins and aging should be considered as factors that influence energy expenditure in mice.

Perinatal bisphenol A exposure promotes hyperactivity, lean body composition, and hormonal responses across the murine life course

“…In addition, the control group displayed a natural decline in spontaneous activity levels throughout the life course (Fig. 2), as previously observed (39).…”

p66Shc deletion or deficiency protects from obesity but not metabolic dysfunction in mice and humans

“…As body mass was reduced but the average adipocyte area was not, adipocyte hyperplasia may be compromised by p66Shc deletion. Previous data showed that p66Shc −/− mice fed a standard diet [14] or a HFD had a normal food intake and a mildly elevated metabolic rate [8], whereas p66Shc deletion affected only the short-term metabolic effects of caloric restriction [15]. Therefore, lipids that are not stored in the adipose tissue are only partly oxidised and accumulate in ectopic sites, such as the liver and skeletal muscle.…”

The influence of Shc proteins and high‐fat diet on energy metabolism of mice

“…Previous work has indicated that EE adjusted for either BW or lean mass is not increased in ShcKO mice maintained on a standard rodent chow diet or subjected to calorie restriction on the same chow diet. [17][18][19] However, there is evidence that ShcKO mice can show increased activation of brown adipose tissue, 20 suggesting that EE could be increased in these mice under certain circumstances.…”