title: Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model.
abstract: Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is associated with numerous pathological conditions. A number of nutritional and hormonal factors have been shown to influence circulating homocysteine concentrations; however, the impact of exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-independent manner. The purpose of this study was to determine the influence of exercise on homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate hyperhomocysteinemia. Female outbred mice (12 weeks old) were assigned to either a sedentary or free-access wheel exercise group. Following a 4-week acclimation period, half of the mice in each group were provided a folate-restricted diet for 7-weeks prior to euthanasia and tissue collection. As expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total homocysteine concentrations; however, exercise completely prevented the increase in circulating homocysteine concentrations. Moreover, exercise reduced plasma homocysteine concentrations 36% within the group fed only the control diet. The prevention of hyperhomocysteinemia by exercise appears, at least in part, to be the result of increased folate-independent homocysteine remethylation owing to a 2-fold increase in renal betaine homocysteine S-methyltransferase. To our knowledge, this is the first report demonstrating the prevention of hyperhomocysteinemia by exercise in a dietary folate-restriction model. Future research will be directed at determining if exercise can have a positive impact on other nutritional, hormonal, and genetic models of hyperhomocysteinemia relevant to humans.
authors.affiliation: Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Neuman
authors.forename: Kelsey A
authors.initials: KA
authors.lastname: Albright
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Schalinske
mesh_terms: D000042:Absorption; D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood*; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000517:prevention & control; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000378:metabolism; D051379:Mice; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D050940:Betaine-Homocysteine S-Methyltransferase