Methionine restriction-induced metabolic changes in C57BL6J mice

Introduction: Eighty percent restriction of normal dietary methionine (MR) intake has been shown to increase energy expenditure and attenuate the rate of adiposity gain in rodents, despite a paradoxical increase in energy intake. Energy expenditure in rats was shown to increase, even though physical activity level stays the same. This observation suggests that metabolic mechanisms account for the majority of increased energy expenditure measured in methionine restricted animals. Purpose: To observe and document the onset of physiological effects brought about and to determine the mechanistic role of the skeletal muscle on MR-induced metabolic changes in the C57BL6J mouse. Methods: C57BL6J mice were fed a control (CON) or MR diet for eight weeks in which food consumption, effect on body composition, physical activity, and energy expenditure were documented. Expression of skeletal muscle genes known to change with increased fatty acid oxidation (UCP3 and CPT1b) were measured post-mortem to determine any mechanistic changes of skeletal muscle fuel utilization. Results: MR-fed C57BL6J mice gain less overall body mass than CON animals, which can be measured within the first few weeks of MR intervention. Additionally, differences in energy expenditure can be measured within the first 14 days. Despite alteration in energy expenditure, MR mice maintain similar levels of activity compared to control animals. Expression of UCP3 and CPT1b, genes associated with increased fatty acid uptake and utilization in skeletal muscle do not change, suggesting increased metabolic affects of other tissues. Conclusion: MR-fed mice exhibit a similar phenotype to that previously reported in rats on MR. Shortly after consumption of MR, C57BL6J mice exhibited an increase in energy expenditure. The increase in energy expenditure in these mice was not influenced by a change in physical activity, or genes associated with increased fatty acid utilization in the skeletal muscle tissue