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

Abstract

The purpose of this study was to determine if Shc proteins influence the metabolic response to acute (7 days) feeding of a high fat diet (HFD). To this end, whole animal energy expenditure (EE) and substrate oxidation were measured in the Shc knockout (ShcKO) and wild-type (WT) mice fed a control or HFD. The activities of enzymes of glycolysis, the citric acid cycle, electron transport chain (ETC), and β-oxidation were also investigated in liver and skeletal muscle of ShcKO and WT animals. The study showed that ShcKO increases (P < 0.05) EE adjusted for either total body weight or lean mass. This change in EE could contribute to decreases in weight gain in ShcKO versus WT mice fed a HFD. Thus, our results indicate that Shc proteins should be considered as potential targets for developing interventions to mitigate weight gain on HFD by stimulating EE. Although decreased levels of Shc proteins influenced the activity of some enzymes in response to high fat feeding (e.g. increasing the activity of acyl-CoA dehydrogenase), it did not produce concerted changes in enzymes of glycolysis, citric acid cycle or the ETC. The physiological significance of observed changes in select enzyme activities remains to be determined.