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No differences were observed in weight gain, food intake, and liver weight of rats assigned to 20C, 20C + DMG, 20CFD, and 20CFD+DMG, indicating that neither folate deprivation nor DMG supplementation affected the aforementioned parameters (Table 1).
Diet Body wt gain
g/28 dFood intake
g/28 dLiver wt % of
body wt20C 101 ± 61 421 ± 21 4.07 ± 0.14 20C + DMG 88 ± 7 439 ± 18 3.99 ± 0.10 20CFD 86 ± 5 402 ± 14 4.14 ± 0.10 20CFD + DMG 100 ± 7 418 ± 14 4.38 ± 0.17 Note. 1Each value is the mean ± SEM, n = 8. Values without a common letter differ, P < 0.05. 20C, 20% casein diet; 20CFD, folate-deprived 20C; different letters are significantly different at P < 0.05. Table 1. Effect of dietary supplementation with N,N-Dimethylglycine (0.1%) on body weight gain, food intake and liver weight in rats fed 20% casein diets with or without folate deficiency
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pHcy concentration was significantly elevated in rats fed folate-deficient diets (20CFD) compared with those fed a folate-sufficient diet (20C): 28.49 ± 0.50 vs. 14.19 ± 0.39 μmol/L (Figure 2A). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 μmol/L) in the 20C group but significantly increased (31.56 ± 0.59 μmol/L) in the 20CFD group.
Figure 2. Effects of supplementation with N,N-dimethylglycine on plasma concentrations of homocysteine (A), cysteine (B), 5-methylterahydrofolate (C), and hepatic concentrations of N,N-dimethylglycine (D) in rats fed control and folate-deprived diets. Each value is presented as the mean ± SEM, n = 8. The means in a panel without a common letter are different, P < 0.05. 20C, 20% casein diet; 20CFD, folate-deprived 20C; DMG, N,N-dimethylglycine; 5-MTHF, 5-methyltetrahydrofolate.
In contrast, plasma cysteine and 5-MTHF levels were significantly higher in the 20C group than in the 20CFD group (Figure 2B and C). DMG supplementation did not show an effect on plasma cysteine levels in both 20C and 20CFD groups. However, DMG supplementation significantly increased plasma 5-MTHF concentration, a quantitative index of folate status[35], in the 20C group but not in the 20CFD group (Figure 2, panel C).
The hepatic concentration of DMG was markedly higher in the 20CFD group than in the 20C group and were unaffected by DMG supplementation (Figure 2D).
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In general, hepatic SAM and SAM/SAH ratio were significantly higher in the fed 20C group, whereas hepatic SAH and Hcy were significantly higher in the 20CFD group (Figure 3). DMG supplementation increased SAM levels in both folate-sufficient and folate-deficient groups, and its effect was significant in the 20C group but not in the 20CFD group (P = 0.05). Moreover, the liver SAM/SAH ratio was significantly higher in the 20CFD+DMG group, but no changes were observed in the 20C+DMG group. DMG supplementation showed no effect on liver Hcy concentration in either folate-deficient or folate- sufficient groups.
Figure 3. Effects of supplementation with N,N-dimethylglycine on hepatic concentrations of S-adenosylmethionine (A), S-adenosylhomocysteine (B), their ratio (C), and homocysteine (D) in rats. Each value is presented as the mean ± SEM, n = 8. The means in a panel without a common letter are different, P < 0.05. SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine. The means in a panel without a common letter are different, P < 0.05. 20C, 20% casein diet; 20CFD, folate-deprived 20C; DMG, N,N-dimethylglycine; 5-MTHF, 5-methyltetrahydrofolate
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The BHMT activity in the liver was similar in all groups (20C, 20C+DMG, 20CFD, and 20CFD+DMG). Rats in the 20C group had significantly higher hepatic MS and CBS activity, as well as hepatic betaine and 5-MTHF levels, than those in the 20CFD group. However, hepatic serine levels in the 20C group were significantly lower than those in the 20CFD group (Figure 4).
Figure 4. Effects of supplementation with N,N-dimethylglycine on hepatic activities of betaine-homocysteine S-methyltransferase (A), methionine synthase (C), and cystathionine β-synthase (E) and hepatic concentrations of betaine (B), 5-methyltetrahydrofolate (D), and serine (F) in rats. Each value is the presented as the mean ± SEM, n = 8. The means in a panel without a common letter are different, P < 0.05. BHMT, betaine-homocysteine S-methyltransferase; CBS, cystathionine β-synthase; MS, methionine synthase; 5-MTHF, 5-methyltetrahydrofolate. The means in a panel without a common letter are different, P < 0.05. 20C, 20% casein diet; 20CFD, folate-deprived 20C; DMG, N,N-dimethylglycine; 5-MTHF, 5-methyltetrahydrofolate
DMG supplementation had no effect on hepatic MS activity in rats fed either 20C or 20CFD. DMG supplementation elevated hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the 20CFD group (Figure 4, panel E). Hepatic betaine was significantly higher in the 20C group than in the fed 20CFD group (1.63 ± 0.12 μmol/g vs. 1.04 ± 0.08 μmol/g). DMG supplementation only slightly increased betaine concentration in both groups (20C+DMG at 1.96 ± 0.16 μmol/g and 20CFD+DMG at 1.39 ± 0.08 μmol/g), but its effects were statistically not significant. DMG supplementation significantly increased hepatic 5-MTHF level and significantly decreased hepatic serine level in the 20C group. On the contrary, no differences were observed in hepatic 5-MTHF and serine levels in the 20CFD+DMG group (Figure 4D and F).
Effect of N,N-Dimethylglycine on Homocysteine Metabolism in Rats Fed Folate-Sufficient and Folate-Deficient Diets
doi: 10.3967/bes2021.047
- Received Date: 2020-09-01
- Accepted Date: 2020-12-04
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Key words:
- Folate deficiency /
- N,N-Dimethylglycine /
- 5-methyltetrahydrofolate /
- Plasma homocysteine
Abstract:
Citation: | LIU Yi Qun, HUANG Ling He, LIU Pei Pei, XING Qing Bin, HAN Feng, WANG Qin, CHEN Shu Rong, SUGIYAMA Kimio, XIANG Xue Song, HUANG Zhen Wu. Effect of N,N-Dimethylglycine on Homocysteine Metabolism in Rats Fed Folate-Sufficient and Folate-Deficient Diets[J]. Biomedical and Environmental Sciences, 2021, 34(5): 356-363. doi: 10.3967/bes2021.047 |