Choline Supplementation Research Articles

Cyclophosphamide- and doxorubicin-induced impairment of high affinity choline uptake and spatial memory can be prevented by dietary choline supplementation in breast tumor bearing mice.

AC chemotherapy (Adriamycin and Cytoxan, i.e., doxorubicin and cyclophosphamide, respectively), a common treatment for breast cancer, can lead to significant cognitive side effects, known as Chemotherapy-Related Cognitive Impairments (CRCIs). These cognitive impairments can persist over 20 years and significantly affect the quality of life for cancer patients and survivors. AC chemotherapy is known to impair ovarian function and reduce circulating estradiol (E2), an effect that can decrease high-affinity choline uptake (HACU) and reduce acetylcholine (ACh) availability. Because ACh is involved in attention, learning and memory function we hypothesized that the cognitive deficits observed during and after adjuvant chemotherapy (AC) are associated with compromised high affinity choline uptake (HACU) due to suppressed ovarian function. Increasing available choline has been demonstrated to enhance HACU under conditions of demand for ACh, therefore we propose that choline supplementation can mitigate CRCIs by maintaining cholinergic function throughout and following chemotherapy treatment. Our study demonstrates cognitive deficits in tumor-bearing but not non-tumor-bearing mice during and following AC chemotherapy, suggesting that tumors enhance vulnerability to CRCIs. We found that HACU was impaired in tumor-bearing mice administered AC chemotherapy and that a choline-enriched diet can mitigate both the reduction of HACU induced by chemotherapy and deficits in spatial memory, suggesting a protective role of dietary choline against disruptions in HACU and cognitive impairment caused by chemotherapy. This underscores the potential use of dietary choline supplementation as a part of chemotherapeutic interventions.

Metabolic status, reproductive, and productive performances of transition dairy cows as affected by dietary rumen-protected choline supplementation.

Research articles about the effects of rumen-protected choline (RPC) supplementation on metabolic response, and reproductive and productive performances in transitional dairy cows were reviewed and presented. Analysis was conducted on 32 research papers that were published. The papers examined treatments without RPC supplementation and RPC supplementation levels varying from 10 to 100 gm/day. The feeding duration of RPC started from 40 to 140 days prepartum and continued until 20 to 140 days postpartum in multiparous dairy cows. Studies indicated that adding herbal choline (Cho) to the diet of transition dairy cows resulted in increased milk production and improved milk quality, leading to enhanced energy balance and reduced oxidative stress. The concentration and yield of IgG in colostrum provide passive immunity to dairy newborns and can be enhanced by dietary Cho supplementation. The inconsistent effects of RPC supplementation on reproduction may be due to several factors such as heat stress, genetics, and management. RPC supplementation improved the transition dairy cows' milk yield and quality, but dosage response was not observed as in the prior publication. Remarkably, the length of RPC supplementation had a positive correlation with an increase in milk yield. Based on this review, 45-50 gm/day dietary RPC supplementation between 3 weeks pre-calving to 8 weeks post-calving is suggested to increase at least 10% milk yield in dairy cows.

Supplementation of Methionine or Choline Did Not Improve Health or Growth Performance in High-Risk, Newly Received Beef Heifers

Supplementation of Methionine or Choline Did Not Improve Health or Growth Performance in High-Risk, Newly Received Beef Heifers

The gut microbe-derived metabolite trimethylamine-N-oxide induces aortic valve fibrosis via PERK/ATF-4 and IRE-1α/XBP-1s signaling in vitro and in vivo

Background and aimsThe gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) has been implicated in the development of cardiovascular fibrosis. Endoplasmic reticulum (ER) stress occurs after the dysfunction of ER and its structure. The three signals PERK/ATF-4, IRE-1α/XBP-1s and ATF6 are activated upon ER stress. Recent reports have suggested that the activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling contributes to cardiovascular fibrosis. However, whether TMAO mediates aortic valve fibrosis by activating PERK/ATF-4 and IRE-1α/XBP-1s signaling remains unclear. MethodsHuman aortic valve interstitial cells (AVICs) were isolated from aortic valve leaflets. PERK IRE-1α, ATF-4, XBP-1s and CHOP expression, and production of collagen Ⅰ and TGF-β1 were analyzed following treatment with TMAO. The role of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in TMAO-induced fibrotic formation was determined using inhibitors and small interfering RNA. ResultsDiseased valves produced greater levels of ATF-4, XBP-1, collagen Ⅰ and TGF-β1. Interestingly, diseased cells exhibited augmented PERK/ATF-4 and IRE-1α/XBP-1s activation after TMAO stimulation. Inhibition and silencing of PERK/ATF-4 and IRE-1α/XBP-1s each resulted in enhanced suppression of TMAO-induced fibrogenic activity in diseased cells. Mice treated with dietary choline supplementation had substantially increased TMAO levels and aortic valve fibrosis, which were reduced by 3,3-dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) treatment. Moreover, a high-choline and high-fat diet remodeled the gut microbiota in mice. ConclusionsTMAO promoted aortic valve fibrosis through activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in vitro and in vivo. Modulation of diet, gut microbiota, TMAO, PERK/ATF-4 and IRE1-α/XBP-1s may be a promising approach to prevent aortic valve fibrosis.

Efficacy and Safety of Prunus mume and Choline in Patients with Nonalcoholic Fatty Liver Disease.

The primary objectives of this study include evaluating changes in lipid profile and liver enzyme levels in nonalcoholic fatty liver disease (NAFLD) patients receiving Prunus mume and choline supplementation (Revolic). Two-hundred patients were recruited from the hepatology outpatient department of a public hospital between January and June 2023. Patients who had confirmed diagnosis of NAFLD, proven with ultrasound (US) followed by biopsy or US alone with age >18 years were included in this study. The study variables were fasting blood sugar, cholesterol levels, low-density lipoprotein (LDL), triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase levels (GGT). All investigations were conducted and compared between baseline, 12 and 24 weeks following treatment. The mean age of all participants was 40.49 ± 10.59 years with 34 males and 166 females. The mean cholesterol levels were reduced to 179.86 ± 35.63 mg/dL from the mean baseline of 197.57 ± 42.52 mg/dL (p = 0.001). There was also a statistically significant difference found between baseline and posttreatment levels of LDL and triglyceride (p < 0.001). The ATL levels were also reduced from baseline 44.91 ± 32.40 U/L to 44.25 ± 30.66 and 41.06 ± 22.15 U/L between 12 and 24 weeks after treatment respectively. There was a statistically significant reduction in ATL, AST, and GGT levels from baseline with p-value < 0.001. The combination of P. mume and choline (Revolic) gives promising results with a significant reduction in lipid profile and liver enzymes. The combination of P. mume and choline can be considered a reliable option for the management of NAFLD due to its efficacy and safety at 24 weeks after treatment as evident in the present study. Butt N, Masood M, Ali A. Efficacy and Safety of Prunus mume and Choline in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2023;13(2):124-127.

Polymorphisms in the choline transporter SLC44A1 are associated with reduced cognitive performance in normotypic but not prenatal alcohol-exposed children

BackgroundCholine is essential for healthy cognitive development. Single nucleotide polymorphisms (SNPs; rs3199966(G), rs2771040(G)) within the choline transporter SLC44A1 increase risk for choline deficiency. In a choline intervention trial of children who experienced prenatal alcohol exposure (PAE), these alleles are associated with improved cognition. ObjectiveThis study aimed to determine if SNPs within SLC44A1 are differentially associated with cognition in children with PAE compared with normotypic controls (genotype × exposure). A secondary objective tested for an association of these SNPs and cognition in controls (genotype-only). DesignThis is a secondary analysis of data from the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Participants (163 normotypic controls, 162 PAE) underwent psychological assessments and were genotyped within SLC44A1. Choline status was not assessed. Association analysis between genotype × exposure was performed using an additive genetic model and linear regression to identify the allelic effect. The primary outcome was the interaction between SLC44A1 genotype × exposure status with respect to cognition. The secondary outcome was the cognitive–genotype association in normotypic controls. ResultsGenotype × exposure analysis identified 7 SNPs in SLC44A1, including rs3199966(G) and rs2771040(G), and in strong linkage (D′ ≥ 0.87), that were associated (adjusted P ≤ 0.05) with reduced performance in measures of general cognition, nonverbal and quantitative reasoning, memory, and executive function (β, 1.92–3.91). In controls, carriers of rs3199966(GT or GG) had worsened cognitive performance than rs3199966(TT) carriers (β, 0.46–0.83; P < 0.0001), whereas cognitive performance did not differ by rs3199966 genotype in those with PAE. ConclusionsTwo functional alleles that increase vulnerability to choline deficiency, rs3199966(G) (Ser644Ala) and rs2771040(G) (3′ untranslated region), are associated with worsened cognition in otherwise normotypic children. These alleles were previously associated with greater cognitive improvement in children with PAE who received supplemental choline. The findings endorse that choline benefits cognitive development in normotypic children and those with PAE.

Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis

Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.

Choline Supplementation in Pregnancy: Current Evidence and Implications

Choline Supplementation in Pregnancy: Current Evidence and Implications

PSIV-18 Combination of 1.8 Mm Choline and Follistatin Supplementation May Reduce Transcript Abundance of CEPT1 and CPBE4 During In-Vitro Bovine Oocyte Maturation

Abstract One-carbon metabolite supplementation during in vitro embryonic development improves blastocyst quality; however, our understanding of the effects of combining these metabolites during in vitro maturation (IVM) is limited. Supplementation with follistatin improved oocyte quality following IVM. Choline supplementation was beneficial during early embryonic development; however, the role of choline during oocyte maturation is unknown. The objective of this study was to investigate the combination of choline and follistatin during IVM on oocyte quality. We hypothesized that supplementation of choline with follistatin would synergistically improve oocyte quality. Follicles (2 to 7mm) were aspirated from slaughterhouse ovaries to obtain cumulus oocyte complexes for IVM that were treated with choline (0, 1.3, or 1.8 mM) and follistatin (0 or 10 ng/mL) in a 3 x 2 design for 23 hr and visually graded for maturation. Cumulus cells and oocytes were used for qPCR transcript abundance analysis (cumulus cells: CHPT1, CX43, EFGR1, FST and STAR; oocytes: BMP15, GDF9, CEPT1, CPBE4, MTHFR, NANOS, CX43 and COX2). Oocyte maturation was analyzed using the GLIMMIX procedure of SAS and transcript abundance was analyzed using the GLM procedure of SAS with the main effect of choline, follistatin and the interaction as fixed effects. There were no differences in the visual characteristics of the oocytes during maturation (P &amp;gt; 0.1). No differences in transcript abundance were observed with choline or follistatin in the cumulus cells (P &amp;gt; 0.1). Addition of 1.3 mM choline during IVM may increase CPEB4 (P = 0.1) in oocytes compared with controls. Transcript abundance of CEPT1 tended to be reduced in oocytes supplemented with 1.8 mM choline and follistatin compared with control oocytes (P = 0.07). Incorporation of follistatin with 1.8 mM choline supplementation during IVM tended (P = 0.08) to reduce CPEB4 in oocytes compared with controls. Other markers of oocyte quality (BMP15, GDF9, NANOS, CX43 and COX2) were not different between choline or follistatin. In contrast to the hypothesis, the combination of choline and follistatin appeared to reduce overall in vitro oocyte quality. While no statistical differences were observed for the other markers, it appears that either 1.3 mM choline or follistatin supplementation may provide a beneficial impact on oocyte quality. Choline 1.3 mM supplementation may improve cell cycle progression from MI to MII phase through the up-regulation of CBEP4. This further supports the conclusion that choline is beneficial for in vitro oocyte development. Although follistatin appears to antagonize the actions of choline during oocyte maturation, they target different mechanisms (TGFβ signaling and DNA methylation, respectively) and both provide long-term benefits during in-vitro embryonic development. Further research is, therefore, warranted to investigate the antagonizing relationship between choline and follistatin during IVM and long-term impacts on blastocyst development. USDA is an equal opportunity provider and employer.

368 Effects of Supplemental Methionine Or Choline on Health and Performance of High-Risk Receiving Beef Heifers

Abstract Methionine and choline are methyl group sources, and their supplementation improves health and immune function in transition dairy cattle. Our objective was to determine if supplemental methionine or choline could improve health and growth performance of newly received growing cattle. In a 3-year experiment, 1,440 crossbred beef heifers (480 per year; 223 ± 4.4 kg initial body weight; Tennessee origin) were received in 15 truckloads (blocks; 5 per year) in October 2020, 2021, and 2022. Individual body weights were measured at arrival. The following day (day 0) cattle were vaccinated for viral and clostridial diseases, received tulathromycin (2.5 mg/kg body weight; Draxxin, Zoetis Inc., Parsippany, NJ), and were stratified within block by arrival body weight to 1 of 8 pens containing 12 animals each. Cattle (40 pens per year; 120 pens total) were limit-fed at 2.2% of body weight daily (dry matter basis) a ration containing 39.5% dry-rolled corn, 40% Sweet Bran (Cargill Corn Milling, Blair, NE), 13% chopped prairie hay, and 7.5% supplement for 60 days; monensin was included at 25 mg/kg diet dry matter. Pens were assigned to 1 of 5 treatments: Control (nothing), 5 g/d methionine (8.33 g/day Smartamine M; Adisseo USA Inc., Alpharetta, GA), 15 g/day methionine (25 g/day Smartamine M), 1.17 g/day choline (26 g/day ReaShure; Balchem Corp., Montvale, NJ), or 3.5 g/day choline (78 g/day ReaShure); treatments were top-dressed at feeding daily. In each year, there were 8 pens per treatment, for a total of 24 pens per treatment across 3 years. Cattle were revaccinated and weighed on day 14, and pen weights were measured weekly thereafter to adjust feed offered the following week. Heifers were observed twice daily for clinical signs of respiratory illness and treated as follows: first morbidity, florfenicol; second morbidity, enrofloxacin; third morbidity, oxytetracycline. Upon third treatment, heifers were declared chronic and removed from the experiment. Performance data from chronic and dead heifers were removed before analysis. Dry matter intake was not affected by treatment (P = 0.48). There were some minor differences among treatments for final body weight, average daily gain, and gain:feed, but none of the treatments were significantly different from Control for these responses. Overall prevalence of respiratory morbidity and mortality were 29% and 0.69%, respectively. No treatment effects were detected for first, second, or third respiratory morbidity or mortality (P ≥ 0.30). Overall, supplemental methionine and choline did not affect growth performance or health of high-risk, newly received heifers.

190 The Nutrigenomic Effects of Dietary Choline and L-Carnitine on the Muscle and Liver of Lean and Overweight Cats

Abstract The objective of this study was to investigate the effects of dietary choline and L-carnitine on the lipotropic gene expression in the muscle and liver of overweight and lean cats, when fed for body weight (BW)maintenance. Overweight [n = 6, body fat percent (BF%): 33.2 ± 1.38] and lean (n = 6, BF%:18.4 ± 0.93), 1-2 year old, male, neutered cats received choline (378 mg/kg BW0.67), L-carnitine (200 mg/kg BW) and no supplementation (control) in a 3x3 Latin square design for 6 weeks, with a 2-week washout between treatments periods. Each treatment was offered with a commercial extruded diet; diet amount was provided to maintain current BW. Cats were anesthetized and quadriceps vastus lateralis (30-50 mg) and liver (30-50 mg) biopsies were harvested after each treatment period using an open muscle or laparoscopic biopsy technique respectively. Tissue RNA was isolated with TRIzol and sequenced using directional PolyA RNA-seq. The expressed genes were aligned using the reference genome, Felis_catus_9.0, Ensembl v.107. Differential gene expression was analyzed for 29,928 genes with SEQUIN, using edgeR and TMM normalization. Pathway analysis was performed using EnrichR databases, BioPlanet 2019 and KEGG 2021. Using a two-group comparison, global analysis revealed 92 and 759 differentially expressed genes in the liver and muscle, respectively of overweight cats compared with lean (P &amp;lt; 0.05). Affected pathways included fat digestion and absorption, including peroxisome proliferator-activated receptor (PPAR) signaling in the liver, and immunity related pathways in muscle (P &amp;lt; 0.05). Upon further analysis using a two-group comparison between overweight and lean cats for each treatment, 11 and 692 significant genes were found in choline treated liver samples and L-carnitine treated muscle samples, respectively (P &amp;lt; 0.05). Similar to the global analysis, genes related to fat metabolism, including PPAR signaling, were significant in the choline treated liver samples, and immunity related genes were significant in the L-carnitine treated muscle samples (P &amp;lt; 0.05). Based on preliminary data, supplemental dietary choline may be beneficial for overweight cats as it may increase fat metabolism in the liver, mitigating risks associated with feline hepatic lipidosis (FHL). Supplemental dietary L-carnitine may also be beneficial due to its effects on immunity related pathways, including pathogen defense. To investigate the full effects of choline and L-carnitine on gene expression, further studies are warranted including older, chronically obese cats, as well as confirmed cases of FHL. Acknowledgements: Natural Sciences and Engineering Council of Canada, Elmira Pet Products and Balchem Corp.

2 Choline as a neurodevelopmental intervention for children with fetal alcohol spectrum disorder: Long-term associations with white matter microstructure and executive function

Objective:Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.Participants and Methods:The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).Results:Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).Conclusions:These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.

Effect of Dietary Betaine, Glycine, and Choline Supplementation on Productive Performance, Egg Quality, Immune Response, and Serum Measurement of Aged Laying Hens Raised under Heat Stress Conditions

Effect of Dietary Betaine, Glycine, and Choline Supplementation on Productive Performance, Egg Quality, Immune Response, and Serum Measurement of Aged Laying Hens Raised under Heat Stress Conditions

Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease

Down syndrome (DS) is a genetic disorder caused by triplication of human chromosome 21. In addition to intellectual disability, DS is defined by a premature aging phenotype and Alzheimer's disease (AD) neuropathology, including septohippocampal circuit vulnerability and degeneration of basal forebrain cholinergic neurons (BFCNs). The Ts65Dn mouse model recapitulates key aspects of DS/AD pathology, namely age-associated atrophy of BFCNs and cognitive decline in septohippocampal-dependent behavioral tasks. We investigated whether maternal choline supplementation (MCS), a well-tolerated treatment modality, protects vulnerable BFCNs from age- and genotype-associated degeneration in trisomic offspring. We also examined the effect of trisomy, and MCS, on GABAergic basal forebrain parvalbumin neurons (BFPNs), an unexplored neuronal population in this DS model. Unbiased stereological analyses of choline acetyltransferase (ChAT)-immunoreactive BFCNs and parvalbumin-immunoreactive BFPNs were conducted using confocal z-stacks of the medial septal nucleus and the vertical limb of the diagonal band (MSN/VDB) in Ts65Dn mice and disomic (2N) littermates at 3–4 and 10–12 months of age. MCS trisomic offspring displayed significant increases in ChAT-immunoreactive neuron number and density compared to unsupplemented counterparts, as well as increases in the area of the MSN/VDB occupied by ChAT-immunoreactive neuropil. MCS also rescued BFPN number and density in Ts65Dn offspring, a novel rescue of a non-cholinergic cell population. Furthermore, MCS prevented age-associated loss of BFCNs and MSN/VDB regional area in 2N offspring, indicating genotype-independent neuroprotective benefits. These findings demonstrate MCS provides neuroprotection of vulnerable BFCNs and non-cholinergic septohippocampal BFPNs, indicating this modality has translational value as an early life therapy for DS, as well as extending benefits to the aging population at large.

Impact of dietary supplementation of choline on blood biochemistry indices and lipid profile of broiler chickens (Cobb 500)

Impact of dietary supplementation of choline on blood biochemistry indices and lipid profile of broiler chickens (Cobb 500)

Enhancing Metabolism and Milk Production Performance in Periparturient Dairy Cattle through Rumen-Protected Methionine and Choline Supplementation.

For dairy cattle to perform well throughout and following lactations, precise dietary control during the periparturient phase is crucial. The primary issues experienced by periparturient dairy cows include issues like decreased dry matter intake (DMI), a negative energy balance, higher levels of non-esterified fatty acids (NEFA), and the ensuing inferior milk output. Dairy cattle have always been fed a diet high in crude protein (CP) to produce the most milk possible. Despite the vital function that dairy cows play in the conversion of dietary CP into milk, a sizeable percentage of nitrogen is inevitably expelled, which raises serious environmental concerns. To reduce nitrogen emissions and their production, lactating dairy cows must receive less CP supplementation. Supplementing dairy cattle with rumen-protected methionine (RPM) and choline (RPC) has proven to be a successful method for improving their ability to use nitrogen, regulate their metabolism, and produce milk. The detrimental effects of low dietary protein consumption on the milk yield, protein yield, and dry matter intake may be mitigated by these nutritional treatments. In metabolic activities like the synthesis of sulfur-containing amino acids and methylation reactions, RPM and RPC are crucial players. Methionine, a limiting amino acid, affects the production of milk protein and the success of lactation in general. According to the existing data in the literature, methionine supplementation has a favorable impact on the pathways that produce milk. Similarly, choline is essential for DNA methylation, cell membrane stability, and lipid metabolism. Furthermore, RPC supplementation during the transition phase improves dry matter intake, postpartum milk yield, and fat-corrected milk (FCM) production. This review provides comprehensive insights into the roles of RPM and RPC in optimizing nitrogen utilization, metabolism, and enhancing milk production performance in periparturient dairy cattle, offering valuable strategies for sustainable dairy farming practices.

Appearance of choline metabolites in plasma and milk when choline is infused into the abomasum with or without methionine

Four lactating, ruminally cannulated Jersey cows, (mean ± standard deviation) 264 ± 54.2 d in milk and 484 ± 24.1 kg of body weight, were arranged in a 4 × 4 Latin square design to measure the effects of abomasal infusion of choline chloride with or without dl-Met on milk and plasma choline metabolites and plasma AA in cows fed a Met-deficient diet. Cows were randomly assigned to 1 of 4 experimental treatments: (1) control; no supplemental Met or choline (CON), (2) 13 g/d of choline ion delivered via abomasal infusion (CHO), (3) 13 g/d of Met delivered via abomasal infusion (MET), and (4) 13 g/d of choline and 13 g/d of Met delivered via abomasal infusion (CHO + MET). Cows received the same basal diet throughout the experiment, which was formulated to be deficient in Met (−5.0 g of Met using the NASEM, 2021, model). Periods were 7 d in length with d 1 to 2 serving as a wash-out period and cows being infused on d 3 to 7. Milk samples were collected twice daily on d 5 to 7 and were analyzed for fat, true protein, lactose, and choline metabolites including betaine, phosphocholine, and free choline using hydrophilic interaction liquid chromatography-tandem mass spectrometry. Blood samples were collected via venipuncture of the coccygeal vein at 1100, 1300, and 1500 h on d 7 of each period and were analyzed for free AA as well as choline metabolites. Plasma Met increased in response to Met infusion and an interaction with choline and Met infusion was observed in the plasma concentration of branched-chain AA. Cows receiving choline exhibited the greatest Cho yield in milk. Milk phosphocholine yield tended to be highest when both choline and Met were infused.

Short-term dietary choline supplementation alters the gut microbiota and liver metabolism of finishing pigs.

Choline is an essential nutrient for pig development and plays a role in the animal's growth performance, carcass characteristics, and reproduction aspects in weaned pigs and sows. However, the effect of choline on finishing pigs and its potential regulatory mechanism remains unclear. Here, we feed finishing pigs with 1% of the hydrochloride salt of choline, such as choline chloride (CHC), under a basic diet condition for a short period of time (14 days). A 14-day supplementation of CHC significantly increased final weight and carcass weight while having no effect on carcass length, average backfat, or eye muscle area compared with control pigs. Mechanically, CHC resulted in a significant alteration of gut microbiota composition in finishing pigs and a remarkably increased relative abundance of bacteria contributing to growth performance and health, including Prevotella, Ruminococcaceae, and Eubacterium. In addition, untargeted metabolomics analysis identified 84 differently abundant metabolites in the liver between CHC pigs and control pigs, of which most metabolites were mainly enriched in signaling pathways related to the improvement of growth, development, and health. Notably, there was no significant difference in the ability of oxidative stress resistance between the two groups, although increased bacteria and metabolites keeping balance in reactive oxygen species showed in finishing pigs after CHC supplementation. Taken together, our results suggest that a short-term supplementation of CHC contributes to increased body weight gain and carcass weight of finishing pigs, which may be involved in the regulation of gut microbiota and alterations of liver metabolism, providing new insights into the potential of choline-mediated gut microbiota/metabolites in improving growth performance, carcass characteristics, and health.

Liver and Muscle Transcriptomes Differ in Mid-Lactation Cows Divergent in Feed Efficiency in the Presence or Absence of Supplemental Rumen-Protected Choline.

Improving dairy cow feed efficiency is critical to the sustainability and profitability of dairy production, yet the underlying mechanisms that contribute to individual cow variation in feed efficiency are not fully understood. The objectives of this study were to (1) identify genes and associated pathways that are altered in cows with high- or low-residual feed intake (RFI) using RNA sequencing, and (2) determine if rumen-protected choline supplementation during mid-lactation would influence performance or feed efficiency. Mid-lactation (134 ± 20 days in milk) multiparous Holstein cows were randomly assigned to either supplementation of 0 g/d supplementation (CTL; n = 32) or 30 g/d of a rumen-protected choline product (RPC; 13.2 g choline ion; n = 32; Balchem Corp., New Hampton, NY, USA). Residual feed intake was determined as dry matter intake regressed on milk energy output, days in milk, body weight change, metabolic body weight, and dietary treatment. The 12 cows with the highest RFI (low feed efficient; LE) and 12 cows with the lowest RFI (high feed efficient; HE), balanced by dietary treatment, were selected for blood, liver, and muscle analysis. No differences in production or feed efficiency were detected with RPC supplementation, although albumin was greater and arachidonic acid tended to be greater in RPC cows. Concentrations of β-hydroxybutyrate were greater in HE cows. Between HE and LE, 268 and 315 differentially expressed genes in liver and muscle tissue, respectively, were identified through RNA sequencing. Pathway analysis indicated differences in cell cycling, oxidative stress, and immunity in liver and differences in glucose and fatty acid pathways in muscle. The current work indicates that unique differences in liver and muscle post-absorptive nutrient metabolism contribute to sources of variation in feed efficiency and that differences in amino acid and fatty acid oxidation, cell cycling, and immune function should be further examined.

Effects of dietary rumen-protected choline supplementation to periparturient dairy cattle on inflammation and metabolism in mammary and liver tissue during an intramammary lipopolysaccharide challenge

The objective of this experiment was to examine the effects of supplementation and dose of rumen-protected choline (RPC) on markers of inflammation and metabolism in liver and mammary tissue during an intramammary lipopolysaccharide (LPS) challenge. Parous Holstein cows were blocked by calving month and randomly assigned within block to receive 45 g/d of RPC (20.4 g/d of choline ions; CHOL45), 30 g/d of RPC (13.6 g/d of choline ions; CHOL30), or no RPC (CON) as a top-dress starting 24 d before expected calving until 21 d postpartum. Cows were alternately assigned within treatment group to either receive an intramammary LPS challenge (200 μg in each rear quarter; Escherichia coli O111:B4) or not at 17 DIM (CHOL45, n = 9; CHOL45-LPS, n = 9; CHOL30, n = 11; CHOL30-LPS, n = 10; CON, n = 10; CON-LPS, n = 9). Hepatic and mammary tissues were collected from all cows on d 17 postpartum. Hepatic and mammary tissues were collected at ∼7.5 and 8 h, respectively, after the LPS challenge. An additional mammary biopsy was conducted on LPS-challenged cows (CHOL45-LPS, CHOL30-LPS, and CON-LPS) at 48 h postchallenge. Hepatic and mammary RNA copy numbers were quantified for genes involved in apoptosis, methylation, inflammation, oxidative stress, and mitochondrial function using NanoString technology. Targeted metabolomics was conducted only on mammary tissue samples (both 8 and 48 h biopsies) to quantify 143 metabolites including choline metabolites, amino acids, biogenic amines and derivatives, organic acids, carnitines, and glucose. Hepatic IFNG was greater in CHOL45 as compared with CON in unchallenged cows, suggesting an improvement in type 1 immune responses. Hepatic CASP3 was greater in CHOL45-LPS as compared with CON-LPS, suggesting greater apoptosis. Mammary IL6 was reduced in CHOL30-LPS cows as compared with CHOL45-LPS and CON-LPS (8 and 48 h). Mammary GPX4 and COX5A were reduced in CHOL30-LPS as compared with CON-LPS (8 h), and SDHA was reduced in CHOL30-LPS as compared with CON-LPS (8 and 48 h). Both CHOL30-LPS and CHOL45-LPS cows had lesser mammary ATP5J than CON-LPS, suggesting that dietary RPC supplementation altered mitochondrial function following LPS challenge. Treatment did not affect mammary concentrations of any metabolite in unchallenged cows, and only 4 metabolites were affected by dietary RPC supplementation in LPS-challenged cows. Mammary concentrations of isobutyric acid and 2 acyl-carnitines (C4:1 and C10:2) were reduced in CHOL45-LPS as compared with CHOL30-LPS and CON-LPS. Taken together, reductions in medium- and short-chain carnitines along with an increase in long-chain carnitines in mammary tissue from CHOL45-LPS cows suggests less fatty acid entry into the β oxidation pathway. Although the intramammary LPS challenge profoundly affected markers for inflammation and metabolism in liver and mammary tissue, dietary RPC supplementation had minimal effects on inflammatory markers and the mammary metabolome.