Homocysteine metabolism, growth performance, and immune responses in suckling and weanling piglets1

Abstract

Homocysteine (Hcy), an intermediary sulfur AA, is recognized as a powerful prooxidant with deleterious effects on physiological and immune functions. In piglets, there is an acute 10-fold increase of plasma concentrations of homocysteine (pHcy) during the first 2 wk of life. This project aimed to maximize pHcy variations within physiological ranges using typical supplies of folates and vitamin B12 (B12) to sows and piglets. Growth, immune response, and Hcy metabolism of piglets were studied until piglets reached 56 d of age. Third-parity sows were randomly assigned to a 2 × 2 split-plot design with 2 dietary treatments during gestation and lactation, S(-) (1 mg/kg folates and 20 µg/kg B12, n = 15) and S(+) (10-fold S(-) levels, n = 16), and 2 treatments to piglets within each half litter, intramuscular injections (150 µg) of B12 (P(+)) at d 1 and 21 (weaning) and saline (P(-)). Within each litter of 12 piglets, 3 P(+) and 3 P(-) piglets were studied for growth and Hcy metabolism, and the others were studied for immune responses. During lactation, plasma B12 decreased and was transiently greater in S(+) vs. S(-) piglets on d 1 and P(+) vs. P(-) piglets on d 7 (sow treatment × age and piglet treatment × age; P < 0.05). From 14 to 21 d of age, pHcy was 33% lower in S(+)P(+) vs. S(-)P(-) piglets (sow treatment × piglet treatment interaction; P < 0.05). At 56 d of age, hepatic B12 was greater and pHcy was lower for P(+) vs. P(-) piglets (P < 0.05). No treatment effect was observed on growth except for a lower postweaning G:F in S(+)P(-) piglets than in others (sow treatment × piglet treatment interaction; P < 0.05). Positive correlations were observed between pHcy and growth (r > 0.29, P < 0.05) before and after weaning. Antibody responses to ovalbumin and serum tumor necrosis factor-α were not affected by treatments, but postweaning serum IL-8 peaked earlier in S(-)P(-) vs. S(+)P(+) piglets (piglet treatment × age; sow treatment × piglet treatment interaction, P < 0.05). Proliferation of lymphocytes in response to the mitogen concanavalin A tended to be lower in culture media supplemented with sera from S(-) vs. S(+) piglets (P = 0.081) and P(-) vs. P(+) piglets (P = 0.098), and the reduction of response was more marked (P < 0.05) with high (>21 µM) compared to medium (17 to 21 µM) or low (<17 µM) pHcy. In conclusion, the present vitamin supplements to sows and/or piglets produced variations of pHcy that were not apparently harmful for growth performance of piglets. The greater pHcy, particularly prevalent in S(-) and/or P(-) piglets, had negative effects on some indicators of immune responses, suggesting that these young animals may be immunologically more fragile.

Oral supplementations of betaine, choline, creatine and vitamin B6 and their influence on the development of homocysteinaemia in neonatal piglets

“…These responses in sows and piglets were associated with remethylation where vitamin B 12 -dependent methionine synthase transfers a methyl group from CH 3 -H 4 -folate to convert Hcy in methionine ( 8 ) . Nevertheless, the lower concentrations of pHcy in these suckling piglets remain two to five times higher than in other species ( 4 , 5 ) . Therefore, other metabolic pathways may be involved for Hcy homeostasis in these animals.…”

“…In the present experiment, it is unlikely that milk folates or vitamin B 12 were limiting because sow diets during gestation and lactation were supplemented at levels of 10 mg/kg of folic acid and 150 µg/kg of cyanocobalamin. Such supplements in sow feed are known to maximise milk transfer of folates ( 23 , 24 ) and vitamin B 12 ( 5 ) to piglets during lactation and reduce the postnatal rise of pHcy in piglets, probably via the cellular methionine synthase remethylation pathway as stated by Simard et al ( 4 ) . Other metabolic pathways for Hcy synthesis or disposal were addressed with the different nutrients used in the present experiment and concentrations of pHcy tended to be lower ( P = 0·09) in treated than in control piglets ( Fig.…”

“…Blood samples were taken when sows were transferred in the farrowing crate, on day 1 of lactation and at weaning. Milk samples were collected on days 1 and 21 of lactation as described by Simard et al ( 4 ) and Audet et al ( 5 ) .…”

“…In suckling piglets, there is a rapid postnatal development of homocysteinaemia ( 3 , 4 ) . This condition is potentially harmful for these young animals as a model comparing two populations of piglets with high (24·7 µ m ) or low (16·7 µ m ) homocysteinaemia showed that indicators of cell-mediated immunity (proliferation of lymphocytes in response to the mitogen concanavalin A) were negatively affected in the former group of piglets, suggesting a weakened immune competence associated with high plasma concentrations of Hcy ( 5 ) .…”

“…Blood plasma total Hcy (pHcy), the most common indicator of Hcy status, decreases in sows and piglets following administration of dietary supplements of folic acid and vitamin B 12 to sows during gestation ( 4 , 6 , 7 ) and lactation ( 5 ) . These responses in sows and piglets were associated with remethylation where vitamin B 12 -dependent methionine synthase transfers a methyl group from CH 3 -H 4 -folate to convert Hcy in methionine ( 8 ) .…”