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Substitution of Dietary Sulfur Amino Acids by dl-2-Hydroxy-4-Methylthiobutyric Acid Reduces Fractional Glutathione Synthesis in Weaned Piglets.

ABSTRACT: BACKGROUND:Cys is limiting for reduced glutathione (GSH) synthesis and can be synthesized from Met. We hypothesized that the dietary Met hydroxyl analogue dl-2-hydroxy-4-methylthiobutyric acid (dl-HMTBA) affects Cys and GSH metabolism and oxidative stress defense differently than Met. OBJECTIVE:The objective was to elucidate whether dl-HMTBA supplementation of a Met-deficient diet affects Cys flux, GSH fractional synthetic rate (FSR), and the basal oxidative stress level relative to Met supplementation in pigs. METHODS:Twenty-nine male German Landrace piglets aged 28 d were allocated to 3 dietary groups: a basal diet limiting in Met (69% of Met plus Cys requirement) supplemented with either 0.15% l-Met (LMET; n = 9), 0.15% dl-Met (DLMET; n = 11), or 0.17% dl-HMTBA (DLHMTBA; n = 9) on an equimolar basis. At age 54 d the pigs received a continuous infusion of [1-13C]-Cys to calculate Cys flux and Cys oxidation. After 3 d, GSH FSR was determined by [2,2-2H2]-glycine infusion, and RBC GSH and oxidized GSH concentrations were measured. At age 62 d the animals were killed to determine hepatic mRNA abundances of enzymes involved in GSH metabolism, GSH concentrations, and plasma oxidative stress defense markers. RESULTS:The Cys oxidation was 21-39% and Cys flux 5-15% higher in the fed relative to the feed-deprived state (P < 0.001). On average, GSH FSR was 49% lower (P < 0.01), and RBC GSH and total GSH concentrations were 12% and 9% lower, respectively, in DLHMTBA and DLMET relative to LMET pigs (P < 0.05). In the feed-deprived state, Gly flux, the GSH:oxidized glutathione (GSSG) ratio, RBC GSSG concentrations, plasma oxidative stress markers, and the hepatic GSH content did not differ between groups. CONCLUSIONS:Although GSH FSR was higher in LMET compared with DLMET or DLHMTBA feed-deprived pigs, these differences were not reflected by lower oxidative stress markers and antioxidant defense enzymes in LMET pigs.

SUBMITTER: Rasch I

PROVIDER: S-EPMC7138682 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Substitution of Dietary Sulfur Amino Acids by dl-2-Hydroxy-4-Methylthiobutyric Acid Reduces Fractional Glutathione Synthesis in Weaned Piglets.

Rasch Ilka I Görs Solvig S Tuchscherer Armin A Viergutz Torsten T Metges Cornelia C CC Kuhla Björn B

The Journal of nutrition 20200401 4

<h4>Background</h4>Cys is limiting for reduced glutathione (GSH) synthesis and can be synthesized from Met. We hypothesized that the dietary Met hydroxyl analogue dl-2-hydroxy-4-methylthiobutyric acid (dl-HMTBA) affects Cys and GSH metabolism and oxidative stress defense differently than Met.<h4>Objective</h4>The objective was to elucidate whether dl-HMTBA supplementation of a Met-deficient diet affects Cys flux, GSH fractional synthetic rate (FSR), and the basal oxidative stress level relative ...[more]

PMID: 31773161

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Project description:BackgroundDL-2-hydroxy-4-methylthiobutyric acid (DL-HMTBA), an L-methionine (L-Met) hydroxyl analogue, has been suggested to be a dietary L-Met source. How dietary DL-HMTBA compared with L-Met affects whole-body L-Met kinetics in growing individuals is unknown.ObjectivesWe determined to what extent DL-HMTBA supplementation of an L-Met-deficient diet affects whole-body L-Met and L-cysteine (L-Cys) kinetics, protein synthesis (PS), and the L-Met incorporation rate in liver protein (L-MetInc) compared with L-Met and DL-Met supplementation in a piglet model.MethodsForty-five, 28-d-old weaned piglets (male, German Landrace) were allocated to 4 dietary groups: L-Met-deficient diet [Control: 69% of recommended L-Met plus L-Cys supply; 0.22% standardized ileal digestible (SID) L-Met; 0.27% SID L-Cys; n = 12] and Control diet supplemented equimolarly to 100% of recommended intake with either L-Met (n = 12; LMET), DL-Met (n = 11; DLMET), or DL-HMTBA (n = 10; DLHMTBA). At 47 d of age, the piglets were infused with L-[1-13C; methyl-2H3]-Met and [3,3-2H2]-Cys to determine the kinetics and PS rates. Plasma amino acid (AA) concentrations, hepatic mRNA abundances of L-Met cycle and transsulfuration (TS) enzymes, and L-MetInc were measured.ResultsDuring feed deprivation, L-Met kinetics did not differ between groups, and were ?3 times higher in the fed state (P < 0.01). Remethylation (RM) was 31% and 45% higher in DLHMTBA than in DLMET and Control pigs, respectively, and the RM:transmethylation (TM) ratio was 50% higher in DLHMTBA than in LMET (P < 0.05). Furthermore, TS and the TS:TM ratio were 32% lower in DLHMTBA than in LMET (P < 0.05). L-MetInc was 42% lower in DLMET and DLHMTBA than in L-Met-deficient Control pigs, whereas plasma AA and hepatic mRNA abundances were similar among DL-HMTBA-, L-Met-, and DL-Met-supplemented pigs.ConclusionsIn piglets, DL-HMTBA compared with L-Met and DL-Met supplementation increases RM and reduces the TS rate to conserve L-Met, but all 3 Met isomers support growth at a comparable rate.

Project description:Development of immune competence in pigs is important for resilience, disease resistance, and performance later in life. Dietary interventions in early life can contribute to immune system development. Use of model dietary interventions, such as diets with a high concentration of zinc, can contribute to the understanding of the interactions between the diet, the intestinal microbiota and intestinal tissues. The aim of the present study was to evaluate the effects of provision of a diet with a high concentration of zinc (Zn, 2690 mg/kg), as model intervention, as compared to provision of a control diet with a regular Zn concentration (100 mg/kg) during a period of nine days during the post weaning period (d 14-23 post weaning (pw)), on the composition of the intestinal microbiota and gene expression in the intestinal mucosa on d 23 and 35 pw (12 d after the termination of the Zn intervention). Whole genome gene expression analysis of the jejunal and ileal mucosa revealed a small overall time-treatment interaction effect at d 23 pw in both intestinal tissues. In both jejunal and ileal mucosa various genes/probes were differentially up or down regulated between treatments. In intestinal tissue samples obtained on d 35 no differences in gene expression were observed. Probes of d 23 pw that were differently expressed and had an annotation were subsequently used as input for further functional analysis using DAVID and Gene Decks databases. The analysis did not result in the identification of gene sets that were differentially expressed between dietary treatments. However, it was shown that a number of upregulated genes in the jejunal mucosa on d 23 pw by the high zinc intervention are involved in pathways related to mineral absorption, immune signalling and cell energy metabolism (glycolysis and gluconeogenesis). A few down regulated genes by the Zn intervention are also involved in immune signalling pathways. It was concluded from the present study that provision of a diet with a high concentration of zinc as zinc oxide during a short period of time (9 days) to piglets in the post weaning period (d 14-23 pw) induces differences on the intestinal expression of genes in part related to the functioning of the local innate immune system. The high dietary zinc intervention can therefore be considered as a suitable model for studying relationships between dietary interventions and development of immune competence in post weaning piglets.

Dataset Information

Substitution of Dietary Sulfur Amino Acids by dl-2-Hydroxy-4-Methylthiobutyric Acid Reduces Fractional Glutathione Synthesis in Weaned Piglets.

Publications

Substitution of Dietary Sulfur Amino Acids by dl-2-Hydroxy-4-Methylthiobutyric Acid Reduces Fractional Glutathione Synthesis in Weaned Piglets.

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