Exercise prevents hyperhomocysteinemia in a folate‐restricted mouse model

Hyperhomocysteinemia resulting from perturbed methyl group and homocysteine (hcy) metabolism has been associated with numerous pathologies, including vascular disease. Currently, the influence of exercise on hcy and methyl group metabolism is not well understood; thus, we used a folate‐restricted mouse model to determine the impact of exercise on hyperhomocysteinemia. Female mice (12 wk old) were assigned to either a sedentary, forced exercise (treadmill), or a free‐access exercise (wheel) group. After an initial 4‐wk training period, half of the mice in each group were fed a folate‐restricted diet for 7 wk and subsequently euthanized for the collection of blood and tissues. Folate‐restriction increased plasma hcy concentrations >2‐fold; however, both treadmill and wheel exercise training completely prevented hyperhomocysteinemia exhibited by the folate‐restricted sedentary mice. Moreover, both forms of exercise decreased hcy concentrations (~35%) in mice fed the control diet. Renal betaine homocysteine S ‐methyltransferase activity was increased >2‐fold by exercise and thus may represent a mechanism whereby exercise prevents hyperhomocysteinemia. To our knowledge, this is the first study to clearly demonstrate the prevention of hyperhomocysteinemia by exercise and will be useful in determining its influence in other nutritional, hormonal, and genetic models of hyperhomocysteinemia. Grant Funding Source : College of Human Sciences, Iowa State University