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. Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is 30 associated with numerous pathological conditions. A number of nutritional and hormonal factors 31 have been shown to influence circulating homocysteine concentrations; however, the impact of 32 exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was 33 that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-34 independent manner. The purpose of this study was to determine the influence of exercise on 35 homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate 36 hyperhomocysteinemia. Female outbred mice (12 wk old) were assigned to either a sedentary or 37 free-access wheel exercise group. Following a 4-wk acclimation period, half of the mice in each 38 group were provided a folate-restricted diet for 7-wk prior to euthanasia and tissue collection. As 39 expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total 40 homocysteine concentrations; however, exercise completely prevented the increase in circulating 41 homocysteine concentrations. Moreover, exercise reduced plasma homocysteine c...

Exercise mitigates the effects of hyperhomocysteinemia on adverse skeletal muscle remodeling.

“…The findings that exercise reverses the effects of HHcy on skeletal muscle dysfunction agree with other studies that exercise decreases or prevents increases in plasma Hcy levels (Neuman et al, 2013;Randeva et al, 2002).…”

“…It has been demonstrated that exercise is capable of lowering Hcy levels, suggesting that exercise can potentially negate the adverse effects of HHcy on different organs (Hrncic et al, 2013;König et al, 2003;Neuman et al, 2013;Randeva et al, 2002;Vincent et al, 2006). Neuman et al stated that exercise was capable of preventing increases in plasma Hcy concentration that were produced by 7 weeks of a folate restricted diet in mouse models (Neuman et al, 2013).…”

“…Neuman et al stated that exercise was capable of preventing increases in plasma Hcy concentration that were produced by 7 weeks of a folate restricted diet in mouse models (Neuman et al, 2013). The low folate diet group that was not exercised displayed significant increases in Hcy levels when compared to non-exercise controls and controls receiving exercise.…”

“…However, the effects of regular exercise on cardiovascular disease and skeletal muscle function are known to be very beneficial. It has also been established that exercise has the capability of reducing homocysteine levels (Neuman et al, 2013;Randeva et al, 2002). Nevertheless, despite the abundance of research on HHcy, there is very little information available regarding the molecular changes that HHcy induces in the skeletal muscle tissue and there is even less information available regarding the effects of exercise on these changes .The present study demonstrates that HHcy induces skeletal muscle fibrosis through induction of inflammatory factors and impairment of perfusion.…”

“…However, the effect of regular exercise on HHcy is not very well established. Recent studies have demonstrated that exercise can lower plasma 3 homocysteine levels and mitigate the adverse effects of HHcy in many organs (Hrncic et al, 2013;König et al, 2003;Neuman, Albright, & Schalinske, 2013;Randeva et al, 2002;Vincent, Bourguignon, & Vincent, 2006). In the current study, we investigated the effects of HHcy on skeletal muscle remodeling and inflammation as well as the ability of exercise to attenuate these effects.…”