Betaine and related compounds: Chemistry, metabolism and role in mitigating heat stress in poultry.

Betaine can operate as an osmolyte and a methyl donor. Betaine is an osmolyte and a methyl donor. Betaine is likewise a zwitterion with osmotic capabilities that can help an animal cope with osmotic stress. Previous investigations have suggested that betaine has various impacts, albeit these studies do not consistently provide the same results. Dietary betaine has received a lot of attention owing to its osmoprotectant, methionine-sparing and antioxidant properties. Betaine is extensively assessed concerning performance and body composition. The tolerance to high temperatures, flock livability, and breast meat output is among the factors frequently mentioned in the literature as being altered by betaine. Betaine, a multi-nutritional agent, may help poultry resist heat stress and poor management. A common subject of betaine research is the idea of betaine saving some methionine. Although research on betaine may not always come to the same results, some discoveries repeat themselves. Because of their effectiveness in increasing growth performance, feed utilization, meat quality, and alleviating heat stress in chicken farms, betaine and methionine are extensively used as feed supplements in poultry diets. This review highlights the influences of betaine on poultry performance, meat quality, carcass characteristics, antioxidant activity, in addition to its role in mitigating heat stress.

Effects of chronic betaine supplementation on performance in professional young soccer players during a competitive season: a double blind, randomized, placebo-controlled trial.

OBJECTIVE: Various nutritional strategies are adopted for athletes to maintain and to improve performance during the competition season. Betaine may enhance performance during a competitive season by increasing the testosterone to cortisol ratio and reducing systemic inflammation. The aim of this study was to investigate the effect of betaine supplementation on the bio-motor abilities in young professional soccer players. METHODS: Twenty-nine young professional soccer players (age, 15.5±0.3 years) were matched by position and randomly assigned to one of two groups for 14 weeks: betaine (BG, 2 g/day; n=14) or placebo (PG n=15). Diet was standardized by a nutritionist, and measures of muscular power (countermovement jump: CMJ), change of direction: modified 5-0-5), acceleration (10 m sprint), sprint performance (30 m sprint time: SpT), muscular strength (leg press and bench press one repetition maximum: 1-RM), repeated sprint ability (running-based anaerobic sprint test: RAST), and aerobic capacity (30-15 intermittent fitness test) were assessed in the pre (P1), mid (P2) and post (P3) season over the course of 5 days. All subjects participated in one soccer match and five training sessions per week. RESULTS: Significant (p < 0.05) group x time interactions were found for maximal oxygen uptake (VO2max), anaerobic peak power, and muscular strength favoring BG at P2 and P3 compared to P1. There were meaningful (p < 0.05) group x time interactions for CMJ, SpT, and peak power during the RAST that favored the BG. CONCLUSIONS: 14-week of betaine supplementation increased predicted 1-RM, VO2max, and repeated sprint ability performance in youth professional soccer players. Betaine supplementation seems to be a useful nutritional strategy to improve and to maintain performance during a competitive soccer season.

Dietary Betaine Mitigates Hepatic Steatosis and Inflammation Induced by a High-Fat-Diet by Modulating the Sirt1/Srebp-1/Pparɑ Pathway in Juvenile Black Seabream (Acanthopagrus schlegelii).

The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway.

Effects of 14-weeks betaine supplementation on pro-inflammatory cytokines and hematology status in professional youth soccer players during a competition season: a double blind, randomized, placebo-controlled trial.

OBJECTIVE: Systemic elevations in pro-inflammatory cytokines are a marker of non-functional over reaching, and betaine has been shown to reduce the secretion of pro-inflammatory cytokines in vitro. The aim of this study was to investigate the effects of betaine supplementation on tumor necrosis factor alpha (TNF-α), interleukins-1 beta (IL-1ß), - 6 (IL-6) and the complete blood cell (CBC) count in professional youth soccer players during a competitive season. METHODS: Twenty-nine soccer players (age, 15.5 ± 0.3 years) were randomly divided into two groups based on playing position: betaine group (BG, n = 14, 2 g/day) or placebo group (PG, n = 15). During the 14-week period, training load was matched and well-being indicators were monitored daily. The aforementioned cytokines and CBC were assessed at pre- (P1), mid- (P2), and post- (P3) season. RESULTS: Significant (p < 0.05) group x time interactions were found for TNF-α, IL-1ß, and IL-6. These variables were lower in the BG at P2 and P3 compared to P1, while IL-1ß was greater in the PG at P3 compared to P1 (p = 0.033). The CBC count analysis showed there was significant group by time interactions for white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and mean corpuscular hemoglobin concentration (MCHC). WBC demonstrated increases at P3 compared to P2 in PG (p = 0.034); RBC was less at P3 compared to P1 in BG (p = 0.020); Hb was greater at P2 compared to P1, whilst it was less at P3 compared to P3 for both groups. MCHC was greater at P3 and P2 compared to P1 in BG, whereas MCHC was significantly lower at P3 compared to P2 in the PG (p = 0.003). CONCLUSION: The results confirmed that 14 weeks of betaine supplementation prevented an increase in pro-inflammatory cytokines and WBC counts. It seems that betaine supplementation may be a useful nutritional strategy to regulate the immune response during a fatiguing soccer season.

The effects of 14-week betaine supplementation on endocrine markers, body composition and anthropometrics in professional youth soccer players: a double blind, randomized, placebo-controlled trial.

OBJECTIVE: Betaine supplementation may enhance body composition outcomes when supplemented chronically during an exercise program. The purpose of this study was to evaluate the effect of betaine supplementation on development-related hormones, body composition, and anthropometrics in professional youth soccer players during a competitive season. METHODS: Twenty-nine players (age, 15.45 ± 0.25 years) were matched based upon position and then randomly assigned to a betaine group (2 g/day; n = 14, BG) or placebo group (PG, n = 15). All subjects participated in team practices, conditioning, and games. If a subject did not participate in a game, a conditioning protocol was used to ensure workload was standardized throughout the 14-week season. Growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol, height, weight, and body composition were assessed at pre-season (P1), mid-season (P2) and post-season (P3). Anthropometric variables were also measured following a one-year follow-up (F). RESULTS: Significant (p < 0.05) group x time interactions were found for testosterone and testosterone to cortisol ratio (T/C). Both variables were greater in BG at P2 and P3 compared to P1, however, the testosterone was less in the PG at P3 compared to P2. There was no significant group by time interactions for GH, IGF-1, lean body mass, or body fat. There was a significant (p < 0.05) group x time interaction in height and weight at F, with the greater increases in BG compared to PG. CONCLUSION: Betaine supplementation increased testosterone levels and T/C ratio in youth professional soccer players during a competitive season. Betaine supplementation had no negative effects on growth (height and weight) and may attenuate reductions in testosterone due to intense training during puberty.

Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family.

Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as Akkermansia muciniphila, Lactobacillus, and Bifidobacterium. In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. Akkermansia muciniphila is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.

Injectable zwitterionic thermosensitive hydrogels with low-protein adsorption and combined effect of photothermal-chemotherapy.

Injectable hydrogels have been developed as biomedical materials in various fields but the biofouling on their surface limits applications in vivo. In this work, a zwitterionic structure was introduced into an injectable hydrogel based on thermosensitive nanogels to overcome the foreign body reaction. The hydrodynamic diameter of the resultant poly(N-isopropylacrylamide-co-sulfobetaine methacrylate) (PNS) nanogels was ca. 105 nm. The aqueous dispersion with a high content of PNS nanogels showed a flowable sol state at room temperature, and turned into a hydrogel in situ at ∼36 °C due to the thermosensitivity of the PNS nanogels. In particular, the resulting hydrogel exhibited lower biofouling both in vitro and in vivo in comparison with similar hydrogels without a zwitterionic structure. Polydopamine nanoparticles (PDA NPs) as a photothermal agent and an anti-tumour drug could be easily co-loaded in the injectable hydrogel. Under near-infrared (NIR) irradiation for 10 min, the temperature of the PNS system containing PDA NPs could reach ca. 38 °C. The drug release from the in situ-forming hydrogel could be accelerated by NIR laser irradiation, and showed a sustainable release behavior and adjustability. The results of intratumoral injection of the as-prepared injectable hydrogel containing PDA NPs and an anti-tumour drug showed significant anticancer effects combining photothermal therapy and local chemotherapy. This constructed injectable zwitterionic thermosensitive hydrogel is easy to use with the advantage of low-fouling and may become a promising platform for various biomedical applications.

Dietary choline, rather than betaine intake, is associated with hepatocellular carcinoma mortality.

The dietary intakes of choline and betaine have been related to the mortality of some neoplasms, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. We examined the associations between dietary choline, five choline-containing compounds, different choline forms, betaine intake and HCC mortality. In total, 905 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort study. Dietary intake was assessed by a valid food frequency questionnaire. Liver cancer-specific mortality (LCSM) and all-cause mortality (ACM) were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox proportional hazards models. It was found that a higher total choline intake was associated with lower ACM, Q4 vs. Q1: HR = 0.72, 95% CI: 0.53-0.97, Ptrend = 0.012 in the fully adjusted model. The associations between total choline intake and LCSM were not significant. Similar associations were found between water-soluble choline intake and HCC mortality, where the fully adjusted HR for ACM was 0.72, 95% CI: 0.53-0.98, Ptrend = 0.017. However, null associations were found between neither phosphatidylcholine (the most abundant lipid-soluble choline) nor total lipid-soluble choline intake and HCC mortality. These results implied that the favorable associations between the total choline intake and ACM were more attributed to water-soluble choline. Furthermore, no significant associations were observed between betaine intake and HCC mortality. Future human intervention trials regarding choline supplementation and liver disease recovery should take the forms into consideration rather than just the total amount alone.

Betaine Supplementation Does Not Improve Muscle Hypertrophy or Strength Following 6 Weeks of Cross-Fit Training.

We aim to investigate the effect of 6 weeks of betaine supplementation on body composition and muscle performance during CrossFit© training. Twenty-nine subjects matched for training status (4.16 0.95 day/week) and body fat mass (12.66 4.08%) were randomly assigned to a betaine (BET; N = 14) or placebo group (PLA; N = 15). Body composition and cellular hydration were estimated with skinfolds measurement and bioelectrical impendence before and after 6 weeks of training. Muscle performance was assessed using three different tests: 3-RM back-squat for muscle strength, 2 km rowing test for aerobic capacity and Bergeron Beep Test for anaerobic capacity. Muscle strength assessed during back squat significantly increased in BET (p = 0.04) but not in the PLA group, however, there were no statistical differences between groups. Although not significant, fat mass was reduced in BET compared to PLA. Overall, body composition and cell hydration measurements did not change in response to training or betaine supplementation. Short-term (6 weeks) betaine supplementation supports muscle strength but was not ergogenic for trained subjects to aerobic and anaerobic performance in the CrossFit©-specific test.

In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy.

PURPOSE: Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes. METHODS: Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes. RESULTS: Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams. CONCLUSION: We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.

Maternal betaine supplementation decreases hepatic cholesterol deposition in chicken offspring with epigenetic modulation of SREBP2 and CYP7A1 genes.

Maternal betaine was reported to regulate offspring hepatic cholesterol metabolism in mammals. However, it is unclear whether and how feeding betaine to laying hens affects hepatic cholesterol metabolism in offspring chickens. Rugao yellow-feathered laying hens (n = 120) were fed basal or 0.5% betaine-supplemented diet for 28 D before the eggs were collected for incubation. Maternal betaine significantly decreased the hepatic cholesterol content (P < 0.05) in offspring chickens. Accordingly, the cholesterol biosynthetic enzymes, sterol regulator element-binding protein 2 (SREBP2) and 3-hydroxy-3-methylglutaryl coenzyme A reductase, were decreased, while cholesterol-7alpha-hydroxylase (CYP7A1), which converts cholesterol to bile acids, was increased at both mRNA and protein levels in betaine-treated offspring chickens. Hepatic mRNA and protein expression of low-density lipoprotein receptor was significantly (P < 0.05) increased, while the mRNA abundance of cholesterol acyltransferase 1 (ACAT1) that mediates cholesterol esterification was significantly (P < 0.05) decreased in the betaine group. Meanwhile, hepatic protein contents of DNA methyltransferases 1 and betaine homocysteine methyltransferase were increased (P < 0.05), which was associated with modifications of CpG methylation on affected cholesterol metabolic genes. Furthermore, the level of CpG methylation on gene promoters was increased (P < 0.05) for sterol regulator element-binding protein 2 and abundance of cholesterol acyltransferase 1 yet decreased (P < 0.05) for cholesterol-7alpha-hydroxylase. These results indicate that maternal betaine supplementation significantly decreases hepatic cholesterol deposition through epigenetic regulation of cholesterol metabolic genes in offspring juvenile chickens.

Dietary betaine improves egg-laying rate in hens through hypomethylation and glucocorticoid receptor-mediated activation of hepatic lipogenesis-related genes.

In avian species, liver lipid metabolism plays an important role in egg laying performance. Previous studies indicate that betaine supplementation in laying hens improves egg production. However, it remains unclear if betaine improves laying performance by affecting hepatic lipid metabolism and what mechanisms are involved. We fed laying hens a 0.5% betaine-supplemented diet for 4 wks to investigate its effect on hepatic lipids metabolism in vivo and confirmed its mechanism via in vitro experiments using embryonic chicken hepatocytes. Results showed that betaine supplemented diet enhanced laying production by 4.3% compared with normal diet, accompanied with increased liver and plasma triacylglycerol concentrations (P < 0.05) in hens. Simultaneously, key genes involved in hepatic lipid synthesis, such as sterol regulatory element binding protein 1 (SREBP-1), fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase 1 (SCD1) were markedly upregulated at the mRNA level (P < 0.05). Western blot results showed that SREBP-1 and SCD1 protein levels were also increased (P < 0.05). Moreover, mRNA expression of main apolipoprotein components of yolk-targeted lipoproteins, apolipoprotein B (ApoB) and apolipoprotein-V1 (ApoV1), in addition to microsomal triglyceride transfer proteins, which is closely related to the synthesis and release of very-low density lipoprotein, were also markedly elevated (P < 0.05). Methylated DNA immunoprecipitation combined with PCR detects reduction of methylation levels in certain regions of the above gene promoters. Chromatin immunoprecipitation PCR assays showed increased binding of glucocorticoid receptor (GR) to SREBP1 and ApoB gene promoters. Similar results of ApoV1 gene expression were obtained from cultured hepatocytes treated with betaine. Additionally, betaine increased the expression of GR and some genes involved in methionine cycle in vitro. These results suggest that betaine supplementation could alter the expression of liver lipid synthesis and transport-related genes by modifying the methylation status and GR binding on their promoter and hence promote the synthesis and release of yolk precursor substances in the liver.

Fetal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in offspring cockerels with modification of promoter DNA methylation.

In documents, maternal betaine modulates hypothalamic cholesterol metabolism in chicken posthatchings, but it remains unclear whether this effect can be passed on by generations. In present study, eggs were injected with saline or betaine at 2.5 mg/egg, and the hatchlings (F1) were raised under the same condition until sexual maturation. Both the control group and the betaine group used artificial insemination to collect sperm from their cockerels. Fertilized eggs were incubated, and the hatchlings of the following generation (F2) were raised up to 64 D of age. F2 cockerels in betaine group showed significantly (P < 0.05) lower body weight, which was associated with significantly decreased (P < 0.05) hypothalamic content of total cholesterol and cholesterol ester. Concordantly, hypothalamic expression of cholesterol biosynthetic genes, SREBP2 and HMGCR, were significantly downregulated (P < 0.05), together with cholesterol conversion-related and excretion-related genes, CYP46A1 and ABCA1. These changes coincided with a significant downregulation in mRNA expression of regulatory neuropeptides including brain-derived neurotrophic factor, neuropeptide Y, and corticotropin-releasing hormone. Moreover, genes involved in methyl transfer cycle were also modified. Betaine homocysteine methyltransferase (P < 0.05) was downregulated, yet DNA methyltransferase1 tended to be upregulated (P = 0.06). S-adenosyl methionine/S-adenosylhomocysteine ratio was higher in the hypothalamus of betaine-treated F2 cockerels, which was associated with significantly modified CpG methylation on the promoter of those affected genes. These results suggested that betaine might regulate central cholesterol metabolism and hypothalamic expression of genes related to brain function by altering promoter DNA methylation in F2 cockerels.

Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.

Effects of Dietary Rumen-Protected Betaine on Lactation Performance and Serum Metabolites of Mid-lactation Holstein Dairy Cows.

This experiment was conducted to investigate the effects of dietary rumen-protected betaine (RPB) supplementation, as partial replacement for methionine, on the lactation performance of mid-lactation dairy cows. A total of 36 Holstein dairy cows were randomly assigned to three groups [control, 20 g/day RPB, or 15 g/day rumen-protected methionine (RPM)]. The experiment was conducted over 9 weeks, with the first week for adaptation. Blood metabolites were analyzed with metabolomics in the control and RPB groups. The results revealed that the milk yield and milk protein content were higher in cows fed RPB and RPM compared to those in the control group. Concentrations of nine metabolites differed between cows in the RPB and control groups. These metabolites were mainly concentrated in six pathways, such as arginine synthesis and proline degradation and cyanoamino acid synthesis. This study revealed that RPB can spare methionine and improve lactation performance of dairy cows fed with diets moderately deficient in methionine.

Low protein diet and methyl-donor supplements modify testicular physiology in mice.

The link between male diet and sperm quality has received significant investigation. However, the impact diet and dietary supplements have on the testicular environment has been examined to a lesser extent. Here, we establish the impact of a sub-optimal low protein diet (LPD) on testicular morphology, apoptosis and serum fatty acid profiles. Furthermore, we define whether supplementing a LPD with specific methyl donors abrogates any detrimental effects of the LPD. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein; n = 8), an isocaloric LPD (LPD; 9% protein; n = 8) or an LPD supplemented with methyl donors (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12; n = 8) for a minimum of 7 weeks. Analysis of male serum fatty acid profiles by gas chromatography revealed elevated levels of saturated fatty acids and lower levels of mono- and polyunsaturated fatty acids in MD-LPD males when compared to NPD and/or LPD males. Testes of LPD males displayed larger seminiferous tubule cross section area when compared to NPD and MD-LPD males, while MD-LPD tubules displayed a larger luminal area. Furthermore, TUNNEL staining revealed LPD males possessed a reduced number of tubules positive for apoptosis, while gene expression analysis showed MD-LPD testes displayed decreased expression of the pro-apoptotic genes Bax, Csap1 and Fas when compared to NPD males. Finally, testes from MD-LPD males displayed a reduced telomere length but increased telomerase activity. These data reveal the significance of sub-optimal nutrition for paternal metabolic and reproductive physiology.

Is the gut microbiota dysbiotic in patients with classical homocystinuria?

Classical homocystinuria (HCU) is characterized by increased plasma levels of total homocysteine (tHcy) and methionine (Met). Treatment may involve supplementation of B vitamins and essential amino acids, as well as restricted Met intake. Dysbiosis has been described in some inborn errors of metabolism, but has not been investigated in HCU. The aim of this study was to investigate the gut microbiota of HCU patients on treatment. Six unrelated HCU patients (males = 5, median age = 25.5 years) and six age-and-sex-matched healthy controls (males = 5, median age = 24.5 years) had their fecal microbiota characterized through partial 16S rRNA gene sequencing. Fecal pH, a 3-day dietary record, medical history, and current medications were recorded for both groups. All patients were nonresponsive to pyridoxine and were on a Met-restricted diet and presented with high tHcy. Oral supplementation of folate (n = 6) and pyridoxine (n = 5), oral intake of betaine (n = 4), and IM vitamin B12 supplementation (n = 4), were reported only in the HCU group. Patients had decreased daily intake of fat, cholesterol, vitamin D, and selenium compared to controls (p < 0.05). There was no difference in alpha and beta diversity between the groups. HCU patients had overrepresentation of the Eubacterium coprostanoligenes group and underrepresentation of the Alistipes, Family XIII UCG-001, and Parabacteroidetes genera. HCU patients and controls had similar gut microbiota diversity, despite differential abundance of some bacterial genera. Diet, betaine, vitamin B supplementation, and host genetics may contribute to these differences in microbial ecology.

Effects of rumen-protected folic acid and betaine supplementation on growth performance, nutrient digestion, rumen fermentation and blood metabolites in Angus bulls.

This study evaluated the effects of rumen-protected folic acid (RPFA) and betaine (BT) on growth performance, nutrient digestion and blood metabolites in bulls. Forty-eight Angus bulls were blocked by body weight and randomly assigned to four treatments in a 2 × 2 factorial design. BT of 0 or 0·6 g/kg DM was supplemented to diet without or with the addition of 6 mg/kg DM of folic acid from RPFA, respectively. Average daily gain increased by 25·2 and 6·29 % for addition of BT without RPFA and with RPFA, respectively. Digestibility and ruminal total volatile fatty acids of neutral-detergent fibre and acid-detergent fibre increased, feed conversion ratio and blood folate decreased with the addition of BT without RPFA, but these parameters were unchanged with BT addition in diet with RPFA. Digestibility of DM, organic matter and crude protein as well as acetate:propionate ratio increased with RPFA or BT addition. Ruminal ammonia-N decreased with RPFA addition. Activity of carboxymethyl cellulase, cellobiase, xylanase, pectinase and protease as well as population of total bacteria, protozoa, Fibrobacter succinogenes and Ruminobacter amylophilus increased with RPFA or BT addition. Laccase activity and total fungi, Ruminococcus flavefaciens and Prevotella ruminicola population increased with RPFA addition, whereas Ruminococcus albus population increased with BT addition. Blood glucose, total protein, albumin, growth hormone and insulin-like growth factor-1 increased with RPFA addition. Addition of RPFA or BT decreased blood homocysteine. The results indicated that addition of BT stimulated growth and nutrient digestion in bulls only when RPFA was not supplemented.

Effects of rumen-protected betaine supplementation on meat quality and the composition of fatty and amino acids in growing lambs.

Rumen-protected betaine (RPB) can enhance betaine absorption in the small intestine of ruminants, while betaine can alter fat distribution and has the potential to affect the meat quality of livestock. Hence, we hypothesized that RPB might also affect the meat quality of lambs. Sixty male Hu sheep of similar weight (30.47 ± 2.04 kg) were selected and randomly subjected to five different treatments. The sheep were fed a control diet (control treatment, CTL); 1.1 g/day unprotected-betaine supplemented diet (UPB); or doses of 1.1 g/day (low RPB treatment; L-PB), 2.2 g/day (middle RPB treatment; M-PB) or 3.3 g/day (high RPB treatment; H-PB) RPB-supplemented diet for 70 days. Slaughter performance, meat quality, fatty acid and amino acid content in the longissimus dorsi (LD) muscle, shoulder muscle (SM) and gluteus muscle (GM) were measured. Compared with CTL, betaine (including UPB and RPB) supplementation increased the average daily weight gain (ADG) (P < 0.05) and average daily feed intake (P < 0.01) of lambs. Rumen-protected betaine increased ADG (P < 0.05) compared with UPB. With increasing RPB doses, the eye muscle area of the lambs linearly increased (P < 0.05). Compared with CTL, betaine supplementation decreased water loss (P < 0.05) in SM and increased pH24 in the SM (P < 0.05) and GM (P < 0.05). Compared with UPB, RPB decreased water loss in the GM (P < 0.01), decreased shear force (P < 0.05) in the LD and SM and increased the pH of the meat 24 h after slaughter (pH24). With increasing RPB doses, the shear force and b* value in the LD linearly decreased (P < 0.05), and the pH24 of the meat quadratically increased (P < 0.05). Compared with CTL, betaine supplementation increased the polyunsaturated fatty acid in the GM (P < 0.05). Compared with UPB, RPB supplementation decreased the saturated fatty acid (SFA) content in the LD (P < 0.05) and increased the unsaturated fatty acids (UFA), mono-unsaturated fatty acids and UFA/SFA ratio in the LD (P < 0.05). Compared with CTL, the content of histidine in the LD increased with betaine supplementation. Compared with UPB, RPB supplementation increased the content of total free amino acids and flavor amino acids in the LD of lambs (P < 0.05). With increasing RPB, the isoleucine and phenylalanine contents in the LD linearly increased (P < 0.05). Overall, the data collected indicated that the meat quality of lambs (especially in the LD) improved as a result of betaine supplementation, and RPB showed better effects than those of UPB.

Grandmaternal betaine supplementation enhances hepatic IGF2 expression in F2 rat offspring through modification of promoter DNA methylation.

BACKGROUND: We reported previously that maternal betaine promotes hepatic insulin-like growth factor (IGF2) expression in F1 offspring rats through hypermethylation of the IGF2/H19 imprinting control region (ICR). It remains unknown whether this acquired trait can be transmitted to the F2 generation. This study aimed to determine whether dietary betaine supplementation to grand dams affects the hepatic IGF2 expression in F2 rat offspring and how it is related to alterations in DNA methylation. F2 rat offspring derived from grand dams fed basal or betaine-supplemented diet (10 g kg-1 ) were examined at weaning. Serum IGF2 concentration was measured with enzyme-linked immunosorbent assay (ELISA). Hepatic expression of IGF2, together with other proliferation and apoptosis markers, was determined by using quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry. The methylation status of the IGF2/H19 ICR and the promoters of IGF2 gene were detected by methylated DNA immunoprecipitation quantitative polymerase chain reaction (MeDIP-qPCR). RESULTS: The maternal betaine-induced up-regulation of hepatic IGF2 expression in F1 rat offspring was transmitted to the F2 generation. The F2 rats from the betaine group demonstrated enhanced hepatic IGF2 expression at both mRNA and protein levels, in association with higher serum IGF2 concentration. No alterations were observed in the ICR methylation of the IGF2/H19 locus, and hypomethylation was detected in promoters of IGF2 gene in betaine group. CONCLUSION: These results indicate that maternal betaine enhances hepatic IGF2 expression in F2 rat offspring through modification of DNA methylation on IGF2 promoters. © 2019 Society of Chemical Industry.