Exercise prevents hyperhomocysteinemia in a folate-deficient mouse model

Abstract

Normal folate, homocysteine, and methyl group metabolism is critical for maintaining optimum health, and perturbations in these mechanisms may lead to a number of pathological conditions such as diabetes, cardiovascular disease, neural tube defects, and cancer. Hyperhomocysteinemia is a condition that occurs when blood plasma concentrations of homocysteine exceed 15μM and has been implicated as an independent risk factor in cardiovascular disease. Specifically, populations with genetic polymorphisms in folatedependent remethylation or poor B-vitamin status are at risk for this condition. This study was conducted in order to determine the influence of exercise on homocysteine and methyl group metabolism in a folate-deficient and -sufficient mouse model. Elevated homocysteine concentrations observed in the folate-deficient sedentary group were reduced by more than 2fold with the addition of both forced treadmill and free access wheel exercise (p < 0.001). Similar results were observed in the folate-sufficient control diet with treadmill and wheel exercised mice having about 50% lower homocysteine concentrations than their sedentary counterparts (p < 0.001). Increased renal homocysteine remethylation through the enzyme betaine-homocysteine S-methyltransferase (BHMT) was observed in wheel exercised mice suggesting an increasingly important role in kidney homocysteine metabolism with exercise (p < 0.05). To our knowledge, this is the first study showing the attenuation of hyperhomocysteinemia in a model known to experience perturbed homocysteine metabolism. Findings from this study will be useful in determining the influence exercise has in other populations of altered homocysteine metabolism such as diabetics, vegans, and individuals with genetic polymorphisms.