Betaine Supplementation Research Articles

Effects of different floor spaces and betaine supplementation on performance and physiology of quails

Decreased productive performance due to heat stress in poultry often occurs in tropical environments. This study seeks to see the body temperature and productive performance of quail in different floor spaces and levels of betaine supplementation. The study was designed as a completely randomized design, consisting of two floor spaces (225 and 164 cm2/bird) and supplementation treatment (0% and 0.15% betaine). ANOVA test and DMRT were applied to catch the effect of treatments. Body temperature measurements showed that rectal and wing temperatures in quail with betaine supplementation were lower than in the control treatment (P<0.05). These results correspond with the betaine group’s feed, protein, and energy efficiency, which is better than the control (P<0.05). The egg production at floor spaces 225 cm2 and 164 cm2 supplemented with betaine was higher than the control groups (P<0.05), with values of 69.55% and 66.49%, respectively. Based on this study, we concluded that betaine supplementation to 225 cm2/bird and 164 cm2/bird floor spaces reduced heat stress and improved laying quail performance.

Metagenomic analysis of non-pathogenic and pathogenic cecal bacteria profiles in quail supplemented with betaine

Cecum microbes are important in utilizing feed nutrients and immunity systems in poultry. This study strived to define the composition of the genus Collinsella, Coriobacteriaceae UCG-002, and Olsenella in the quail cecum supplemented with different betaine schemes. The treatment consisted of 3 levels, namely: control (C); C+0.12% betaine supplementation (B1); and B1–0.12% betaine supplementation (B2). This study used a completely randomized design with three replications. The next-generation sequencing method of the 16S rRNA gene region V3-V4 was applied to view the taxonomy profile of microbes (Threshold: 0.8~1). The relative abundance of the genera Collinsella, Coriobacteriaceae UCG-002, and Olsenella were analyzed using ANOVA and Duncan’s test on R software. The results showed that the provision of B1 increased genus Collinsella and Coriobacteriaceae UCG-002 more than C and B2 (p<0.05). A significant decrease occurred in treatment B1 compared to treatment C indicated in the genus Olsenella as a pathogenic bacterium in the quail cecum (p<0.05). The B2 treatment showed the relative abundance of the genera Collinsella, Coriobacteriaceae UCG-002, and Olsenella tended to return to the microbial composition of treatment C. This study concluded that giving B1 improved the genus Collinsella, Coriobacteriaceae UCG-002, and Olsenella in the quail cecum tract.

Shift of Choline/Betaine Pathway in Recombinant Pseudomonas for Cobalamin Biosynthesis and Abiotic Stress Protection.

The B12-producing strains Pseudomonas nitroreducens DSM 1650 and Pseudomonas sp. CCUG 2519 (both formerly Pseudomonas denitrificans), with the most distributed pathway among bacteria for exogenous choline/betaine utilization, are promising recombinant hosts for the endogenous production of B12 precursor betaine by direct methylation of bioavailable glycine or non-proteinogenic β-alanine. Two plasmid-based de novo betaine pathways, distinguished by their enzymes, have provided an expression of the genes encoding for N-methyltransferases of the halotolerant cyanobacterium Aphanothece halophytica or plant Limonium latifolium to synthesize the internal glycine betaine or β-alanine betaine, respectively. These betaines equally allowed the recombinant pseudomonads to grow effectively and to synthesize a high level of cobalamin, as well as to increase their protective properties against abiotic stresses to a degree comparable with the supplementation of an exogenous betaine. Both de novo betaine pathways significantly enforced the protection of bacterial cells against lowering temperature to 15 °C and increasing salinity to 400 mM of NaCl. However, the expression of the single plant-derived gene for the β-alanine-specific N-methyltransferase additionally increased the effectiveness of exogenous glycine betaine almost twofold on cobalamin biosynthesis, probably due to the Pseudomonas' ability to use two independent pathways, their own choline/betaine pathway and the plant β-alanine betaine biosynthetic pathway.

Single nucleotide polymorphism C994g of the cytochrome P450 gene possess pleiotropic effects in Bos taurus, L.

The chronic consumption of mycotoxin-contaminated forage tends to the weight loss of young cattle, decreasing the reproductive success of adult animals, milk yield, and tolerance to high temperatures. The aim of this paper was to study the eff ects of the SNP C994G in the CYP3A28 gene on the productive and reproductive characteristics of dairy and beef breeds. Cows were measured by body weight dynamics, exterior, reproduction, milk production traits, bone mineral density, bulls were analyzed estimating their progeny traits. Dairy cows received dietary betaine supplement with the measurement of homocysteine levels. Molecular genetic was performed by PCR-RFLP method. The effects of SNP C994G were shown in relation to the udder size, the constitution and birth weight of Abredin-Angus cows, as well as the fat and protein content of Ukrainian Red-and-White Dairy cows milk. The higher sensitivity of the GG genotype to less homocysteine level after the addition of betaine was shown. Given the identifi ed correspondence, pleiotropic eff ects of CYP3A28 gene can be concluded. A microscopic analysis of forage supported the findings in relation to greater efficiency of the CC genotype under conditions of low mycotoxins contamination, to which CYP3A28 is selective.

Effects of three feed attractants on the growth performance and meat quality of the largemouth bass (Micropterus salmoides)

The trial was conducted to investigate the effects of limonene, allicin and betaine supplementation in low fish meal (FM) diet on growth performance, antioxidant capacity, meat quality and intestinal health in largemouth bass (M. salmoides). The biting-balls test and feeding trial were successively conducted. For the one, the results of the biting-ball test showed that with the increase of the concentration of the three attractants, the attracting effect firstly increased, then decreased, and the effect reached maximum at 0.2% concentration. (P &amp;lt; 0.05). Further, a 9-week feeding trial was conducted using five diets, including a basal diet with 30% and 40% fish meal without attractant, 30% fish meal supplemented with 0.2% limonene, 0.2% allicin or 0.2% betaine (the diets were named FM30, FM40, FM30 + L, FM30 + A, FM30 + B, respectively). The results demonstrated that adding limonene, allicin and betaine at concentration of 0.2% to the low fish meal feed could improve final body weight, weight gain rate, and specific growth rate of M. salmoides but only in 4 weeks (P &amp;gt; 0.05). Besides, dietary supplementation with attractants could significantly reduce the content of MDA in serum and liver, and increase the activity of GSH in liver (P &amp;lt; 0.05). Compared with FM30 group, the supplementation with limonene, allicin or betaine diet had higher pH, redness (a*), yellowness (b*) (P &amp;gt; 0.05), and lower refrigeration loss, cooking loss values (P &amp;lt; 0.05). Furthermore, supplementation with attractants groups had higher values for villus height, lamina propria, crypt depth, submucous layer, and serous layer (P &amp;lt; 0.05). Taken together, these results indicated that limonene, allicin and betaine had a time effect on the growth performance, and could improve antioxidant capacity, meat quality and intestinal health of M. salmoide.

Betaine: A Potential Nutritional Metabolite in the Poultry Industry

Simple SummaryThe effects of antibiotics as alternative feed additives on the health of poultry have gained promising results. Betaine has been extensively used in the poultry industry as a potential metabolite. This review article focuses on the interaction between betaine and other elements, such as methionine, choline, and creatine. In addition, poultry carcass traits and performance, as well as its osmoregulatory, anticoccidial, immune-modulatory, and heat-stress alleviation activities, were discussed with regard to the effects of dietary supplementation of betaine. Due to the different advantages of using betaine, it has been suggested to be a promising feed additive to the poultry diet. More research is needed to explain how betaine exerts its action in the body.Poultry industry has been recognized as a fast-developing sector aiming to produce low-cost and high-nutrient foods for human consumption. This review article aimed to focus on the significant roles of dietary betaine supplementation in the poultry industry. In this respect, different effects of betaine on performance and carcass traits, as well as its osmoregulatory, anticoccidial, immune-modulatory, and heat-stress alleviation activities, were discussed. Different concentrations of betaine supplementation can improve the feed conversion ratio, final body weight, breast muscle yield, egg production ratio, and reduce body fat contents in broiler chicken, turkey, duck, geese, and quail diets. Betaine supplemented with methyl groups can eliminate the need to have some methyl-group donors, including choline and methionine, therefore having positive effects on feed conversion ratio in poultry diets. The osmolytic character of betaine can alleviate heat stress and have a positive impact on tonic immobility, which consequently reduces stress in poultry. By inhibiting distinct developmental stages of Eimeria species, betaine reduces the damaging effects of coccidiosis on broiler chickens and improves intestinal structure and function. The immunological, cardiovascular, neurological, renal, and hepatic metabolic systems benefit from betaine’s osmo-protective properties. Therefore, betaine has the potential to be considered as an alternative to feed additives and enhances the health status and productive performance of poultry.

Betaine Ameliorates Acute Sever Ulcerative Colitis by Inhibiting Oxidative Stress Induced Inflammatory Pyroptosis.

Betaine rich in beet is used as an important source of human nutrition. Here this study aims to explore whether betaine supplementation can protect against acute sever ulcerative colitis (ASUC) and the underlying mechanism METHODS AND RESULTS: ASUC model is induced by dextran sulfate sodium (DSS), and effects of betaine as a methyl donor on ASUC are evaluated. Betaine mitigates the changes, for example, elevated DAI, weight loss, spleen enlargement, colon shortening, and disordered colonic mucosa. The protective effects of betaine on colonic barrier integrity in ASUC are then verified through examining tight junction proteins by western blot and immunofluorescence. Spectrophotometry method and western blot confirm that betaine can decrease levels of oxidative markers (MDA, MPO, NOS, and COX2), and promote expressions of antioxidant proteins (GSH, NRF2, CAT, and SOD1). Further, betaine prevents colonic inflammatory pyroptosis by blocking expressions of NLRP3 inflammasome complex (NLRP3, ASC, and cleaved-caspase 1), N terminal-GSDMD, and release of relevant inflammatory factors. Betaine inhibits colonic oxidative stress induced inflammatory pyroptosis to alleviate ASUC, which shows therapeutic potential against colitis and other acute inflammatory disorder.

341 Effects of Supplemental Betaine on Protein Deposition and Plasma Amino Acid Concentrations in Growing Steers with Modulated Methyl Group Status

Abstract Methyl group donors (e.g., methionine, betaine) may improve performance of growing beef cattle. Our objective was to evaluate effects of betaine supplementation on protein deposition and plasma amino acids in growing steers with altered methyl group status. Seven ruminally cannulated Holstein steers (189 kg) were used in a 6×6 Latin square design with 10-d periods. Factorial treatments were continuously infused abomasally and included 3 methyl group modulators [MGM; control; 15 g/d guanidinoacetic acid (GAA); or 16.8 g/d creatine] and 2 levels of betaine (0 or 5.7 g/d betaine). Supplemental GAA or creatine increases body creatine supply; however, GAA consumes methyl groups during creatine synthesis, whereas creatine spares methyl groups by reducing GAA synthesis. Steers received 3.5 kg/d (DM basis) of a corn-based diet. Total collection of urine and feces occurred on d 7 through 9 to measure N retention. Jugular blood was collected on d 10. No interactions between MGM or betaine were observed (P≥0.17). Betaine supplementation increased retained N (P=0.03), but did not affect urinary or fecal N excretion (P≥0.16). Betaine increased plasma Met (P=0.03) and cystine (P=0.04) and tended to decrease plasma Lys (P=0.10). Nitrogen retention was not affected by MGM (P=0.63). Creatine increased urinary N (P=0.04), and GAA tended to increase urinary N (P=0.08). Creatine increased fecal N excretion relative to control (P=0.02); GAA also increased fecal N relative to control (P&amp;lt; 0.01). Plasma Met was not affected by MGM (P=0.41). Plasma cystine was decreased by creatine relative to control (P=0.01), but was not affected by GAA relative to control (P=0.26). Plasma Lys was decreased by GAA (P&amp;lt; 0.01) and creatine (P=0.05) relative to control. Supplemental betaine improved protein deposition in growing steers and altering methyl group status affected plasma amino acid concentrations.

Effect of Betaine Supplementation to Methionine-deficient Diet on Growth Performance, Carcass Characteristics, Blood Parameters and Economic Efficiency of Broilers

Background: Betaine is a protein found in shellfish, spinach and wheat bran. Betaine’s main physiological function is to act as a methyl donor and an osmolyte. Betaine also functions as an osmolyte, ensuring that the avian’s cellular water and ion balance are maintained. It may protect a variety of intestinal bacteria against osmotic changes resulting in increased microbial fermentation activity. Adding betaine to chicken diets has been shown to improve nutritional digestibility and lower abdominal fat weight. Methods: A total of two hundred and seventy day-old commercial broiler chicks were randomly allotted to nine treatments of six equal replicates with 5 chicks each (9 x 6 x 5=270). Nine experimental isonitrogenous and isocaloric diets consisting of a control diet (CD), 25% and 50% methionine deficient diet and with graded levels of betaine (0.1, 0.2 and 0.3% levels) were formulated and fed to chicks from 1 to 42 days of age. Result: The results of the study revealed that supplementation of betaine to broiler diets deficient in methionine at 25% and 50% resulted in better performance with (p less than 0.05) higher body weight gain and better FCR, higher percentages of livability, carcass yield, total edible parts, breast yield and breast meat while those of heart and abdominal fat were decreased but relative weights of giblets, liver and gizzard were not affected compared with their control counterparts. Betaine supplementation resulted in increased immunity against ND, better tolerance to oxidative stress and better net profit over feed cost of broilers at 42 days of age.

Comparing effects of natural betaine and betaine hydrochloride on gut physiology in broiler chickens

Betaine is a well-known component of poultry diets with various effects on nutritional physiology. For example, increased water retention due to the osmolytic effect of betaine increases the volume of the cell, thereby accelerating the anabolic activity, integrity of cell membrane, and overall performance of the bird. Betaine is a multifunctional component (trimethyl derivative) acting as the most efficient methyl group donor and as an organic osmolyte, which can directly influence the gastrointestinal tract integrity, functionality, and health. So far, nothing is known about the effect of betaine on the intestinal barrier in chickens. In addition, little is known about comparing natural betaine with its synthetic form. Therefore, an animal study was conducted to ascertain the effects of betaine supplementation (natural and synthetic) on performance and intestinal physiological responses of broilers. One hundred and five 1-day-old broiler chicks were randomly assigned into 3 groups with 35 birds each: control, natural betaine (1 kg active natural (n)-betaine/ton of feed) and synthetic (syn)-betaine‐HCL (1 kg active betaine /ton of feed). Histological assessment showed lower jejunal crypt depth and villi height/crypt depth ratio in syn-betaine-HCL group compared with natural n-betaine fed birds. Furthermore, it was found that syn-betaine-HCL negatively affects the integrity of the intestine by increasing the intestinal paracellular permeability in both jejunum and cecum as evidenced by a higher mannitol flux. Additionally, syn-betaine-HCl significantly upregulated the IFN-γ mRNA expression at certain time points, which could promote intestinal permeability, as it plays an important role in intestinal barrier dysfunction. Body weight (BW) and body weight gain (BWG) did not differ (P > 0.05) between the control birds and birds supplemented with syn-betaine‐HCL. However, the BW and BWG were significantly (P < 0.05) improved by the dietary inclusion of n-betaine compared with other treatments. Altogether, the dietary inclusion of n-betaine had a positive effect on performance and did not negatively affect gut paracellular permeability. Furthermore, our results show that syn-betaine-HCl induces changes in the intestine, indicating an alteration of the intestinal histology and permeability. Thus, natural or synthetic betaine has different effects, which needs to be considered when using them as a feed supplement.

The Impacts Of Combined Blood Flow Restriction Training And Betaine Supplementation On Exercise-associated Serum Hormones

The Impacts Of Combined Blood Flow Restriction Training And Betaine Supplementation On Exercise-associated Serum Hormones

Preloaded Betaine Supplementation On Thermoregulation, Fluid Balance, And Cycling Performance In Heat: A Pilot Study

Preloaded Betaine Supplementation On Thermoregulation, Fluid Balance, And Cycling Performance In Heat: A Pilot Study

Effects of betaine on growth performance, intestinal health, and immune response of goslings challenged with lipopolysaccharide

The objective of this experiment was to investigate the effects of betaine on growth performance, serum parameters, intestinal health, and immune performance of goslings in response to lipopolysaccharide (LPS) challenge. A total of 168 healthy male 15-day-old Jiangnan White Goslings were randomly divided into 4 groups, with 6 replicates per treatment and seven goslings per replicate. A 2 × 2 factorial arrangement included 2 factors, that is, LPS challenge (injection of LPS or physiological saline) and betaine (added 0 or 0.06% betaine in diet). The results indicated that LPS challenge significantly reduced the average daily feed intake (ADFI), average daily gain (ADG), and body weight (BW) at 21 D of the goslings, while dietary betaine supplementation tended to increase the ADFI during the LPS stress period (P = 0.08) and BW at 21 D of the goslings (P = 0.09). The LPS-challenged goslings showed higher pro-inflammatory cytokines (interleukin-1 [IL-1β], interleukin-6 [IL-6], tumor necrosis factor-α (TNF-α), and Interferon-gamma [IFN-γ]) and lower anti-inflammatory cytokine (Interleukin-10 [IL-10]) (P < 0.05) at 21 D of age. Dietary betaine supplementation alleviated LPS-induced increase in pro-inflammatory cytokines. The LPS challenge significantly decreased duodenal and jejunal villus height (VH) and villus height and crypt depth ratio (VCR), while the addition of betaine significantly increased duodenal VH and VCR (P < 0.05). On the other hand, addition of betaine significantly alleviated decline of enzyme activity on lipase, amylase, trypsin, and chymotrypsin in the intestinal of goslings. The LPS challenge significantly increased the content of serum D-lactic acid (D-LA) and the activity of diamine oxidase (DAO) at 21 D of the goslings. The LPS challenge and betaine addition significantly increased the mRNA expression of Occcludin (OCLN) in jejunal mucosa at 28 D of the goslings (P < 0.05). In conclusion, our research demonstrated that betaine can alleviate the decline of growth performance and immune performance in goslings caused by LPS. The results also indicate betaine possesses anti-inflammation properties and improves intestinal barrier functions. We recommend that 0.06% betaine be added into the diet to improve the intestinal health and immune performance of goslings.

Concurrent betaine administration enhances exercise-induced improvements to glucose handling in obese mice

Background and aimsBetaine supplementation has been shown to enhance hepatic lipid metabolism in obese mice and improve exercise performance in healthy populations. We examined effects of betaine supplementation, alone or in combination with treadmill exercise, on the metabolic consequences of high fat diet (HFD)-induced obesity in mice. Methods and resultsMale C57BL/6 J mice were fed chow or HFD. After 15 weeks, HFD mice were split into: HFD, HFD with betaine (1.5% w/v), HFD with treadmill exercise, and HFD with both betaine and exercise (15 m/min for 45min, 6 days/week; n = 12/group) for 10 weeks. Compared to HFD mice, body weight was significantly reduced in exercise and exercise-betaine mice, but not in mice given betaine alone. Similarly, adiposity was reduced by exercise but not by betaine alone. HFD-induced glucose intolerance was slightly improved by exercise, but not with betaine alone.Significantly greater benefits were observed in exercise-betaine mice, compared to exercise alone, such that GTT-outcomes were similar to controls. This was associated with reduced insulin levels during ipGTT, suggesting enhanced insulin sensitivity. Modest benefits were observed in fatty acid metabolism genes in skeletal muscle, whilst limited effects were observed in the liver. HFD-induced increases in hepatic Mpc1 (mitochondrial pyruvate carrier 1) were normalized by all treatments, suggesting potential links to altered glucose metabolism. ConclusionsOur data show that drinking 1.5% betaine was sufficient to augment metabolic benefits of exercise in obese mice. These processes appear to be facilitated by altered glucose metabolism, with limited effects on hepatic lipid metabolism.

Betaine Reduces Lipid Anabolism and Promotes Lipid Transport in Mice Fed a High-Fat Diet by Influencing Intestinal Protein Expression.

Betaine is more efficient than choline and methionine methyl donors, as it can increase nitrogen storage, promote fat mobilisation and fatty acid oxidation and change body fat content and distribution. Lipid is absorbed primarily in the small intestine after consumption, which is also the basis of lipid metabolism. This study was conducted to establish a mouse model of obesity in Kunming mice of the same age and similar body weight, and to assess the effect of betaine on the intestinal protein expression profile of mice using a proteomic approach. Analysis showed that betaine supplementation reversed the reduction in expression of proteins related to lipid metabolism and transport in the intestine of mice induced by a high-fat diet (HFD). For example, the addition of betaine resulted in a significant upregulation of microsomal triglyceride transfer protein (Mttp), apolipoprotein A-IV (Apoa4), fatty-acid-binding protein 1 (Fabp1) and fatty-acid-binding protein 2 (Fabp2) expression compared to the HFD group (p < 0.05), which exhibited accelerated lipid absorption and then translocation from the intestine into the body’s circulation, in addition to a significant increase in Acetyl-CoA acyltransferase (Acaa1a) protein expression, hastening lipid metabolism in the intestine (p < 0.05). Simultaneously, a significant reduction in protein expression of alpha-enolase 1 (Eno1) as the key enzyme for gluconeogenesis in mice in the betaine-supplemented group resulted in a reduction in lipid synthesis in the intestine (p < 0.05). These findings provide useful information for understanding the changes in the protein profile of the small intestine in response to betaine supplementation and the potential physiological regulation of diets’ nutrient absorption.

The Effect of 3-Week Betaine Supplementation on Blood Biomarkers of Cardiometabolic Health in Young Physically Active Males.

Betaine (BET) supplementation decreases homocysteine concentration in plasma, but it may also have an adverse effect on health by increasing blood lipid concentrations, at least in overweight and obese individuals. The aim of this study was to evaluate the effect of BET supplementation on the lipid profile and concentrations of homocysteine, inflammatory cytokines, and liver enzymes in physically active, healthy males. This was a randomized, placebo (PL)-controlled, double-blinded, crossover trial. BET (2.5 or 5.0 g/d) was administered for 21 days. Before and after supplementation with BET or PL, anthropometric measurements and blood were collected in a fasted state. Our results show that BET supplementation significantly decreased homocysteine concentration (from 17.1 ± 4.0 μmol/L before BET to 15.6 ± 3.5 μmol/L after BET, p = 0.009, η2 = 0.164). However, the intervention had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerol, interleukins 1β and 6, and tumour necrosis factor α concentrations, or alanine and aspartate activities. In addition, there were no interactions between the MTHFR genotype and BET dose. In conclusion, BET supplementation may be beneficial for homocysteine concentration in healthy, physically active males, with no detrimental effect on lipid profile.

Effects of 6-Week Betaine Supplementation on Muscular Performance in Male Collegiate Athletes.

Simple SummaryBetaine supplementation has ergogenic potential for exercise performance, but the effect of betaine supplementation in combination with training for 6 weeks is still unclear. The present study aimed to investigate the effects of betaine supplementation on muscular power and maximal strength in collegiate male athletes. The participants in the study received either 5 g/day of betaine or placebo for 6 weeks, during which they maintained their regular exercise training. The overhead medicine-ball throw, countermovement jump, and one repetition-maximum of a bench press, overhead press, half squat, and sumo dead lift by the participants were assessed before and after betaine supplementation. Blood lipids were also analyzed before and after betaine supplementation. We found that receiving 5 g of betaine supplementation daily during the 6-week preparatory period had extra benefits on the power of the upper body and maximal strength on the half squat and overhead press. Betaine seems to be a useful nutritional strategy to improve and maintain performance during 6-week preparatory periods in collegiate athletes.The purpose of this study was to investigate the effects of 6-week betaine supplementation during a preparatory period of collegiate athletes on muscular power and strength. Sixteen male collegiate athletes received 5 g/day of betaine (betaine group, n = 9) or carboxymethyl cellulose (placebo group, n = 7) for 6 weeks. All participants engaged in their regular training during the experimental period. The overhead medicine-ball throw (OMBT), countermovement jump, and maximal strength (one repetition maximum, 1-RM) on the bench press, overhead press, half squat, and sumo dead lift by the participants were assessed before and after betaine supplementation. Blood lipids were also analyzed before and after betaine supplementation. After supplementation, there were no significant differences between betaine and placebo groups on any variables. Compared to presupplementation, the performance of OMBT and 1-RM of overhead press and half squat in the betaine group had significantly improved (p < 0.05). By contrast, no significant differences were observed in the placebo group before and after supplementation. Blood analysis revealed no negative effect on blood lipid profiles. Betaine seems to be a useful nutritional strategy to improve and maintain performance during 6-week preparatory periods in collegiate athletes.

The Role of Betaine in Patients With Chronic Kidney Disease: a Narrative Review.

This narrative review aimed to explore the functions of betaine and discuss its role in patients with chronic kidney disease (CKD). Some studies on CKD animal models have shown the benefits of betaine supplementation, including decreased kidney damage, antioxidant recovery status, and decreased inflammation. Betaine (N-trimethylglycine) is an N-trimethylated amino acid with an essential regulatory osmotic function. Moreover, it is a methyl donor and has anti-inflammatory and antioxidant properties. Additionally, betaine has positive effects on intestinal health by regulating the osmolality and gut microbiota. Due to these crucial functions, betaine has been studied in several diseases, including CKD, in which betaine plasma levels decline with the progression of the disease. Low betaine levels are linked to increased kidney damage, inflammation, oxidative stress, and intestinal dysbiosis. Furthermore, betaine is considered an essential metabolite for identifying CKD stages.

MiR-143-Mediated Responses to Betaine Supplement Repress Lipogenesis and Hepatic Gluconeogenesis by Targeting MAT1a and MAPK11.

The liver as the central organ is responsible for lipogenesis, gluconeogenesis and one-carbon metabolism. Methyl donors (e.g., betaine) modulate metabolic homeostasis and gene regulation through one-carbon metabolism. MiR-143 regulates DNA methylation by targeting DNMT3A, thereby suggesting that this miRNA participates in one-carbon metabolic pathways. However, the effect and mechanism that regulate glucose and lipid metabolism via the methyl group metabolism pathway remain elusive. In this study, we found that a betaine supplement and miR-143 KO significantly promoted lipolysis and glucose utilization and repressed lipogenesis and gluconeogenesis through enhancing energy consumption and thermogenesis, repressing GPNMB and targeting MAPK11, respectively. We further explored the relationship between miR-143 and a methyl donor (betaine) and the miR-143-mediated responses to the betaine supplement regulating the mechanism of the glucose and lipid metabolism. The results showed that betaine significantly down-regulated the expression of miR-143 that subsequently increased SAM levels in the liver by targeting MAT1a. In brief, the regulations of glucose and lipid metabolism are related to the miR-143-regulation of one-carbon units, and the relationship between betaine and miR-143 in the methionine cycle is a typical yin-yang type of regulation. Thus, betaine and miR-143 function together as key regulators and biomarkers for preventing and diagnosing metabolic diseases such as fatty liver disease, obesity, and diabetes.

Betaine Promotes Fat Accumulation and Reduces Injury in Landes Goose Hepatocytes by Regulating Multiple Lipid Metabolism Pathways.

Simple SummaryBetaine is a safe, effective, naturally occurring trimethylglycine, which is widely used as a nutritional supplement in animal husbandry. Early research showed betaine redistributes body fat by regulating systemic fatty acid metabolism. We previously found that betaine reduces sebum thickness and abdominal fat, and increases liver weight and triglyceride content, in Landes geese fed with high-energy carbohydrates. However, the mechanism underlying these effects remained unclear. Here, we present an in vitro Landes goose fatty liver model, which was developed using primary hepatocytes and a high-glucose medium simulating the conditions of high-energy carbohydrate feeding in vivo. We used this model to investigate the effects of betaine supplementation. Our results suggest that betaine increases lipid deposition, reduces lipid droplet size, and restores mitochondrial membrane potential (β-oxidation) and the expression of genes involved in lipid hydrolysis transfer genes. By contrast, the expression of fatty acid synthesis genes was down-regulated. The comprehensive effect led to an increase in total triglyceride in the liver, but a healthier steatosis phenotype. Overall, these results show that betaine could improve the quality of foie-gras while decreasing the injury to geese that results from overfeeding.Betaine is a well-established supplement used in livestock feeding. In our previous study, betaine was shown to result in the redistribution of body fat, a healthier steatosis phenotype, and an increased liver weight and triglyceride storage of the Landes goose liver, which is used for foie-gras production. However, these effects are not found in other species and strains, and the underlying mechanism is unclear. Here, we studied the underpinning molecular mechanisms by developing an in vitro fatty liver cell model using primary Landes goose hepatocytes and a high-glucose culture medium. Oil red-O staining, a mitochondrial membrane potential assay, and a qRT-PCR were used to quantify lipid droplet characteristics, mitochondrial β-oxidation, and fatty acid metabolism-related gene expression, respectively. Our in vitro model successfully simulated steatosis caused by overfeeding. Betaine supplementation resulted in small, well-distributed lipid droplets, consistent with previous experiments in vivo. In addition, mitochondrial membrane potential was restored, and gene expression of fatty acid synthesis genes (e.g., sterol regulatory-element binding protein, diacylglycerol acyltransferase 1 and 2) was lower after betaine supplementation. By contrast, the expression of lipid hydrolysis transfer genes (mitochondrial transfer protein and lipoprotein lipase) was higher. Overall, the results provide a scientific basis and theoretical support for the use of betaine in animal production.