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

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 < .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 an 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 (eg, 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. SIGNIFICANCE OF THE STUDY: We report higher EE in ShcKO versus WT mice when consuming the HFD. Although decreased levels of Shc proteins influenced the activity of a central enzyme of β-oxidation in response to high-fat feeding, it did not produce concerted changes in enzymes of glycolysis, citric acid cycle, or the ETC. Thus, an increase in EE in response to consumption of an HFD may be a mechanism that leads to decreased weight gain previously reported in ShcKO mice with long-term consumption of an HFD.