Dietary Methionine Research Articles

Effect of increasing dietary methionine-to-lysine ratio during early gestation on fetal development and piglet birth weight

It was hypothesized that increasing dietary methionine (Met) for sows in early gestation would have a positive effect on fetal and placental growth and development, thereby also increasing the birth weight of piglets. The objective of the study was to investigate the effect of increasing the total dietary methionine-to-lysine ratio (Met:Lys) from 0.29 (Control diet) to 0.41 (Met diet) from mating to day 50 of gestation. A total of 349 multiparous sows were allocated to either the Control or Met diet group. The sows’ backfat thickness was measured pre-farrowing, post-farrowing, and at weaning in the previous cycle and on days 14, 50 and 112 of gestation in the current cycle. On day 50, three Control and six Met sows were slaughtered. In 116 litters, piglets were weighed and measured individually at farrowing. The dietary treatment did not affect the sows’ backfat thickness before or during gestation (P > 0.05). The number of liveborn and stillborn piglets at farrowing were similar in both groups (P > 0.05) and no differences in average piglet birth weight, total litter weight at birth or within-litter variation in birth weight (P > 0.05) were observed. In conclusion, increasing the dietary Met:Lys ratio for sows in early gestation had no effect on piglet birth weight.

Evaluation of Increasing Concentrations of Supplemental Choline Chloride on Modern Broiler Chicken Growth Performance and Carcass Characteristics.

Choline has been demonstrated to partially substitute methionine in broiler chicken diets due to their interconnected biosynthesis pathways. Yet, research on the impacts of dietary choline supplementation on modern strains of high-yielding broilers is limited. The objective was to evaluate the effect of increasing additions of choline chloride on the performance and carcass characteristics of broilers fed reduced methionine diets and reared under summer environmental conditions. Ross 708 x Yield Plus male broilers were reared for 41 days on used litter in floor pens (n = 2232; 31 birds per pen). Birds were fed one of six corn and soybean meal-based, reduced methionine diets containing 0, 400, 800, 1200, 1600, or 2000 mg of added choline chloride per kg of feed. Diets were provided in three phases. On day 43, 10 birds per pen were processed. Increasing dietary choline resulted in similar body weight gain, reduced feed intake, and improved feed efficiency. Choline chloride supplementation linearly increased both breast and carcass yields while concomitantly increasing the incidence and severity of wooden-breast-affected fillets. These results indicate that supplementing reduced-methionine broiler diets with choline chloride during high environmental temperatures may improve feed efficiency and increase carcass and breast yields but may also increase wooden breast.

Protective Effects of Methionine on some Physiological and Biochemical Parameters of Triton-Stressed Male Rats

The aim of this study is to find out the effect of amino acid methionine 35 mg/kg of feed with the diet to minimize the harms caused by oxidative stress resulting from treatment with Triton at a dose of (300 ml/kg) on physiological and biochemical parameters. This study was conducted at the Technical Institute/Mosul for the period 1/12/2021 - 1/2/2022 to find out the protective effects of the amino acid methionine on some physiological and biochemical parameters of Triton-stressed white male laboratory rats, as their weight ranged from 180-220 g and their ages ranged between 12- 14 weeks. After confirming that they are free of diseases, with the help of a veterinarian. Some biochemical parameters were measured, namely, glucose, cholesterol T.C., triglycerides T.G, (LDL-c) low-density lipoprotein cholesterol, (VLDL-c) very low-density lipoprotein cholesterol, (HDL-c) high-density lipoprotein cholesterol, and the atherogenic index. In this study, were used 24 white male rats, distributed randomly into four groups of 6 rats/group. And it was as follows: Control group: was injected a 1 ml of distilled water to equalize the stress of holding the rats. Triton group: They were injected with Triton 300 ml/kg body weight of Triton. Methionine group: was given (35 mg/kg diet) of the amino acid methionine and triton methionine group: they were injected with triton (300 ml/kg body weight) and methionine amino acid at (35 mg/kg diet) concentration. Dosing process took place daily for a period of (8) weeks.The study showed a significant decrease at the probability value (P≤0.05) in the concentration of each of cholesterol, triglycerides, LDL-c, VLDL-c, the atherogenic index, and glucose, however, HDL-c levels were found to be higher in this group compared to the control group. Treatment with methionine also led to an improvement in some physiological and biochemical parameters of rats that were subjected to triton stress. Keywords: methionine, triton, lipoproteins, atherogenic index.

Zinc Status of Horses and Ponies: Relevance of Health, Horse Type, Sex, Age, and Test Material

Little is known about the animal- and diet-related factors that could interfere with the plasma zinc (Zn) concentrations of equines. Additionally, the adequacy of plasma to reflect changes in the Zn intake is unclear. In the first part of this study, the plasma Zn concentrations of hospitalized horses and ponies (n = 538) were measured and evaluated for the impact of the age, sex, horse type, and internal diseases of the animals. In the second part, the effects of increasing dietary Zn chloride hydroxide and Zn methionine supplementations were assessed on the plasma and mane hair Zn concentrations of healthy horses (n = 2) and ponies (n = 8). Part 1: The age, sex, and horse type did not influence the plasma Zn concentrations. No effect of internal diseases was observed, with the exception of higher plasma Zn concentrations in animals with metabolic disorders compared to the control group (p < 0.05). Part 2: Both Zn supplements dose-dependently increased the Zn concentrations in the mane hair (p = 0.003), but not in the plasma of the horses and ponies. In conclusion, the plasma Zn concentrations were widely unaffected by nutritional and non-nutritional factors in equines, while mane hair samples better reflected the dietary Zn supply.

Licorice extract inhibits the cGAS-STING pathway and protects against non-alcoholic steatohepatitis.

Background: Inflammation and fibrosis are typical symptoms of non-alcoholic steatohepatitis (NASH), which is one of the most common chronic liver diseases. The cGAS-STING signaling pathway has been implicated in the progression of NASH, and targeting this pathway may represent a new therapeutic strategy. Licorice is a widely used herb with anti-inflammatory and liver-protective properties. In this study, we assessed the effect of licorice extract on the cGAS-STING pathway. Methods: Bone marrow-derived macrophages (BMDMs) were treated with licorice extract and then stimulated with HT-DNA, 2'3'-cGAMP, or other agonists to activate the cGAS-STING pathway. Quantitative real-time PCR and western blot were conducted to analyze whether licorice extract could affect the cGAS-STING pathway. Methionine and choline-deficient diet (MCD) was used to induce NASH in mice, which were treated with licorice extract (500mg/kg) by gavage and/or c-176 (15mg/kg) by intraperitoneal injection every 2days. After 6weeks of treatment, histological analysis of liver tissue was performed, along with measurements of plasma biochemical parameters. Results: Licorice extract inhibits cGAS-STING pathway activation. Mechanistically, it might function by inhibiting the oligomerization of STING. Treatment with licorice extract reduced inflammation and fibrosis in MCD diet-induced NASH mice models. Furthermore, we found that the therapeutic effect of combination treatment with licorice extract and C-176 (STING inhibitor) on the pathology and fibrosis of MCD diet-induced NASH models was similar to that of licorice extract or C-176 administered alone. Conclusion: Licorice extract can inhibit the cGAS-STING pathway and improve hepatic inflammation and fibrosis in NASH mice models. It strongly suggests that licorice extract may be a candidate therapeutic for NASH.

Abstract 1095: Exploiting altered methionine metabolism to overcome treatment resistance in glioblastoma

Abstract Glioblastoma (GBM) is the most aggressive adult brain tumor and is uniformly fatal due to resistance to standard therapies such as radiation (RT) and chemotherapy. Our group and others have identified altered metabolism as a key mediator of GBM RT resistance. Methionine is an essential sulfur-containing amino acid that cells use to synthesize antioxidants, polyamines and S-adenosyl methionine (SAM), which drives intracellular methylation reactions. Methionine uptake is dramatically elevated in GBM compared to normal brain, but what GBMs use this methionine for, and whether it governs GBM treatment resistance, is unknown. Here, we find that RT acutely increases the levels of numerous methionine-related metabolites in multiple RT-resistant GBM models. To interrogate metabolic pathway activity, we used 13C5 methionine stable isotope tracing to show that GBMs respond to RT by activating the conversion of methionine to SAM, which is dependent on signaling through the DNA damage response. We developed in vivo methionine stable isotope tracing techniques to confirm these findings in orthotopic PDX models of GBM. Blocking the conversion of methionine to SAM, through pharmacologic inhibition of methionine adenosyltransferase 2A (MAT2A), slowed the repair of RT-induced DNA damage and increased cell death in GBM models following RT. These effects were especially pronounced in GBM models lacking the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP). Pharmacologic inhibition of MAT2A in flank and orthotopic in vivo GBM models depleted SAM levels and slowed tumor growth when combined with RT. Combining MAT2A inhibition with dietary methionine restriction and RT slowed GBM tumor growth even further. Together, our work demonstrates a new signaling link between DNA damage and methionine-driven SAM synthesis in GBM. Inhibiting SAM synthesis slows the repair of RT-induced DNA damage and augments RT efficacy. This therapeutic strategy may be especially effective in GBMs defective in methionine salvage and spare normal cortex in which methionine salvage is active. Citation Format: Navyateja Korimerla, Kari-Wilder Romans, Peter Kalev, Ayesha Kothari, Nathan Qi, Charles Evans, Maureen Kachman, Marc L Hyer, Katya Marjon, Taryn Sleger, Daniel R Wahl. Exploiting altered methionine metabolism to overcome treatment resistance in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1095.

Dietary Methionine Restriction Improves Gastrocnemius Muscle Glucose Metabolism through Improved Insulin Secretion and H19/IRS-1/Akt Pathway in Middle-Aged Mice

Methionine restriction (MR) improves glucose metabolism. In skeletal muscle, H19 is a key regulator of insulin sensitivity and glucose metabolism. Therefore, this study aims to reveal the underlying mechanism of H19 upon MR on glucose metabolism in skeletal muscle. Middle-aged mice were fed MR diet for 25 weeks. Mouse islets β cell line β-TC6 cells and mouse myoblast cell line C2C12 cells were used to establish the apoptosis or insulin resistance model. Our findings showed that MR increased B-cell lymphoma-2 (Bcl-2) expression, deceased Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate-specific proteinase-3 (Caspase-3) expression in pancreas, and promoted insulin secretion of β-TC6 cells. Meanwhile, MR increased H19 expression, insulin Receptor Substrate-1/insulin Receptor Substrate-2 (IRS-1/IRS-2) value, protein Kinase B (Akt) phosphorylation, glycogen synthase kinase-3β (GSK3β) phosphorylation, and hexokinase 2 (HK2) expression in gastrocnemius muscle and promoted glucose uptake in C2C12 cells. But these results were reversed after H19 knockdown in C2C12 cells. In conclusion, MR alleviates pancreatic apoptosis and promotes insulin secretion. And MR enhances gastrocnemius muscle insulin-dependent glucose uptake and utilization via the H19/IRS-1/Akt pathway, thereby ameliorating blood glucose disorders and insulin resistance in high-fat-diet (HFD) middle-aged mice.

Effects of Soy Lecithin Supplementation on Liver Lipid Profile and Oxidative Stress of Rats Receiving Methionine and Choline Deficient Diet

Effects of Soy Lecithin Supplementation on Liver Lipid Profile and Oxidative Stress of Rats Receiving Methionine and Choline Deficient Diet

Dietary choline can partially spare methionine to improve the feeds utilization and immune response in juvenile largemouth bass (Micropterus salmoides): Based on phenotypic response to gene expression

Present study was conducted to explore the interrelationship between dietary methionine and choline in feed formulations for largemouth bass (Micropterus salmoides). Four isonitrogenous (51.0%) and isolipidic (14.0%) diets were formulated supplemented or not supplemented with methionine and choline: NC diet (basic diet), Met diet (basic diet supplemented with methionine), Cho diet (basic diet supplemented with choline) and PC diet (basic diet supplemented with methionine and choline). Fish with an initial body weight of 8.01 ± 0.08 g were fed with each diet for 8 weeks. Significant interactions were found between dietary methionine and choline on growth performance, plasma nutrient concentration, genes expression level of nutrient sensing signaling pathways, nutrient metabolism and immune response. Dietary methionine addition had great effects on improving weight gain rate (WGR), specific growth rate (SGR) and Feed efficiency ratio (FER), while choline supplementation only increased FER (P＜0.05). Both added methionine and choline had higher WGR, SGR and FER than the other groups (P＜0.05). Moreover, compared with NC group, PC, Met and Cho groups also activated growth hormone/insulin-like growth factor (GH-IGF), mammalian target of rapamycin (mTOR) pathway and shut down amino acid response (AAR) pathway to further enhanced glucose, lipid synthesis (P＜0.05). Dietary choline and methionine were similar in regulating the activity of signaling pathways (P > 0.05). Supplemented both together had the most significant effect on promoting nutrient accumulation and improving feed efficiency (P＜0.05). Furthermore, methionine and choline addition also enhanced the gene expression level of key regulators in immune response. Combined supplementation could improve this effect than the individual supplementation to a certain degree. Therefore, when methionine met the requirement of largemouth bass, choline supplementation could further raise the utilization of methionine and partially spare methionine efficiently. This study provided a more reasonably method for using choline to improve growth and feed utilization which could maximize growth and avoid the toxic effect of excessive methionine addition in diets.

Intestinal permeability, microbiota composition, and expression of genes related to intestinal barrier function of broiler chickens fed different methionine sources supplemented at varying concentrations

Intestinal health of broiler chickens is influenced by the concentration of dietary amino acids but data are limited on the role of dietary methionine (Met). Two experiments were conducted to investigate the implications of different Met sources for performance, gut barrier function, and intestinal microbiota in broilers. In the first experiment, Ross 308 off-sex birds (n=900) were assigned to 10 dietary treatments each replicated 9 times in a 35-day study. Three sources of Met included DL-Met, L-Met, or Met hydroxy analog free acid (MHA-FA), each supplemented at suboptimal (SUB) at 80%, adequate (ADE) at 100% and over-requirement (OVR) at 120% of the specifications against a deficient (DEF) diet with no added Met. The second experiment used 96 Ross 308 broilers in a 2×4 factorial arrangement. Four diets included 3 sources of Met supplemented at ADE level plus the DEF treatment. On d 17, 19, and 23, half of the birds in each dietary treatment were injected with dexamethasone (DEX) to induce leaky gut. In the first experiment, without an interaction, from d 0 to 35, birds fed DL-Met and L-Met performed similarly for BWG, feed intake, and FCR but birds fed MHA-FA had less feed intake and BWG (P < 0.05). At d 23, mRNA expression of selected tight junction proteins was not affected except for claudin 2. Ileal microbiota of DEF treatment was different from DL-MET or L-MET supplemented birds (P < 0.05). However, microbiota of MHA-FA treatments was only different at OVR from the DEF group. The abundance of Peptostreptococcus increased in DEF treatment whereas Lactobacillus decreased. In the second experiment, DEX independently increased (P < 0.001) intestinal permeability assayed by fluorescein isothiocyanate dextran, but diet had no effect. DL-Met and L-Met fed birds had a higher level of claudin 3 only in DEX-injected birds (P < 0.05). In conclusion, unlike the level of supplementation, DL-Met, L-Met, and MHA-FA were largely similar in their limited impacts on intestinal barrier function and gut microbiota in broilers.

Effect of Methionine and Age of Rat on the Occurrence of Hemorrhagic Diathesis in Rats Fed a Ration Containing Irradiated Beef

There was no mortality in weanling Sprague-Dawley rats fed non-irradiated beef. A significant (P < 0.01) number of deaths occurred in the group fed the irradiated-beef ration. Methionine reduced the mortality rate linearly (P < 0.01). The prothrombin rate (reciprocal of prothrombin time × 1000) of rats fed an irradiated-beef ration was lower (P < 0.01) than that for rats fed a ration containing nonirradiated beef. The prothrombin rate increased (P < 0.01) when the ration was supplemented with methionine. Growth was depressed (P < 0.01) by dietary methionine. Some adult Sprague-Dawley rats died of internal hemorrhages when fed a ration containing nonirradiated beef, indicating adults were more susceptible than weanling rats to hemorrhagic diathesis. Feeding irradiated beef increased the mortality (P < 0.01), but it was decreased (P < 0.01) by supplemental methionine. The methionine required to prevent hemorrhagic disease in adult rats fed nonirradiated-beef diet was less (P < 0.01) than that of rats fed irradiated beef. Feeding irradiated beef decreased the prothrombin rate (P < 0.01) and supplementation with methionine increased the rate (P < 0.01). There was a linear (P < 0.01) decrease of body weight gain with increasing supplemental methionine, which was less (P < 0.05) for rats fed non-irradiated beef than for those fed irradiated-beef rations.

Response of Rainbow Trout (Oncorhynchus mykiss) Growing from 50 to 150 g to Supplements of DL-Methionine in a Semipurified Diet Containing Low or High Levels of Cystine

We studied the effect of increasing dietary concentrations of DL-methionine on growth, feed intake, feed conversion ratio and the composition of gain in rainbow trout. Twenty-four groups of 20 trout initially weighing 51 ± 0.5 g/trout were fed semipurified diets containing 20.1 MJ digestible energy and either 3.0 or 5.8 g cystine/kg dry matter. At each level of cystine, 12 levels of methionine (2 to 11 g/kg dry matter) were achieved by supplementation with graded quantities of DL-methionine. During an experiment of 49 feeding days, no significant effect of the level of dietary cystine was found for any performance trait. Nonlinear responses to increasing dietary methionine concentrations were found for feed intake, growth rate, protein concentration of gain and protein deposition, whereas fat concentration of gain decreased concurrently. Dietary methionine was utilized most efficiently at a concentration of 3.5 g methionine/kg dry matter or 0.17 g/MJ digestible energy. Ninety-five percent of the plateau deposition of body protein was achieved at a dietary methionine concentration of 8 g/kg dry matter or 0.40 g/MJ digestible energy. For achieving 98%, the required concentration was 9.0 g/kg or 0.49 g/MJ. Recommended dietary methionine concentration will depend on the trait chosen.

Вплив лікувально-профілактичної кормової добавки на рубцеву ферментацію хворих на кетоз корів

It is known that ionophoric antibiotics regulate ruminal fermentation, improve the utilization of feed protein, and prevent the occurrence of ketosis and steatosis in ruminants. Ionophoric antibiotics and β-acids of hops have a similar spectrum of biological activity, that is, they inhibit the vital activity of most gram-positive microorganisms of the rumen. Bacteria, like other living organisms, need vitamin E as an active antioxidant for cell membranes. The toxicity of tocopherol is very low, so adding it to the diet of ruminants in larger quantities can stimulate celluloselytic rumen bacteria and compensate for the negative effect of ionophores on fiber breakdown. Since rumen bacteria break down a significant part of dietary choline, methionine and carnitine, ruminants must receive them in a protected form, so their influence on rumen fermentation is insignificant. Three groups of cows of the Ukrainian dairy black-spotted breed with milk yields of 5 or more thousand kg during the previous lactation were formed: with signs of clinical ketosis — 4 animals; with subclinical ketosis — 5 animals and clinically healthy — 5 animals. For a month, cows with ketosis were given a treatment supplement containing crushed granules of hop cones (20 g), vitamin E (3 g), and rumen protected choline (50 g), methionine (20 g) and carnitine (1 g). Clinically healthy cows were used as control. In the blood of cows with subclinical ketosis, the additive increased the concentration of glucose and decreased the concentration of β-hydroxybutyrate, these indicators were within the normal range. In cows with symptoms of clinical ketosis, using of the feed additive also reduced the concentration of β-hydroxybutyrate (P&lt;0.01), but it was still higher than normal. In sick cows, amylolytic and lipolytic activity was lower than in healthy cows (P&lt;0.05–0.01). Celluloselytic activity was lower only in cows with clinical ketosis. The proteolytic activity of rumen content changed in the opposite way; it was higher in sick cows (P&lt;0.05–0.01). This is a consequence of the increase in the number and activity of hyper producing ammonia bacteria in the rumen, what is characteristic for ketosis. After treatment of cows with subclinical ketosis, the celluloselytic and amylolytic activities in the rumen fluid were equal to the corresponding indicators of healthy cows, and the proteolytic activity was even slightly lower (P&lt;0.05) than in the control group. Treatment of cows with clinical form of ketosis was not as effective, although the general trends remained. During subclinical and clinical ketosis, a greater amount of ammonia was found in the rumen fluid (P&lt;0.05–0.01), because of higher proteolytic activity. In both forms of ketosis, the concentration of volatile fatty acids in the rumen decreased, and the concentration of lactate increased (P&lt;0.05–0.01). After the treatment, these indicators in cows with subclinical ketosis approached the healthy animals, while the condition of cows with clinical ketosis improved, but the concentration of ammonia continued to differ from healthy animals.

Revaluating the dietary methionine requirements in an improved strain of nile tilapia (Oreochromis niloticus)

It has been shown with terrestrial animals that the genetic improvement increases the nutrient requirements of the animal, which becomes more efficient in using these nutrients to achieve their higher growth potential. This study was conducted to estimate the dietary methionine requirements of different generations of the Genetically Improved Farmed Tilapia (GIFT) strain of Nile tilapia at the juvenile stage (17.51 g–19.55 g initial body weight). To achieve this objective, a completely randomized 2 × 6 factorial design was applied, with the genetic background of fish (generation) as the first independent variable with two levels, the 16th and 17th generations, and the methionine content of the diet as the second independent variable, with 6 graded levels, 0.52, 0.62, 0.84, 0.94, 1.04 and 1.27% of methionine in the diets, respectively. At the end of the 42-day experiment, the interaction effect of the generation × diet was not significant (P > 0.05) for any of the response parameters studied. The genetic improvement led to 15% more growth in the 17th generation than the 16th generation of the GIFT strain of Nile tilapia, which was accompanied with better feed conversion ratio, protein productive value, and energy productive value in the former generation (P < 0.05). Whatever the generation considered, the optimum dietary methionine requirement for the growth of the improved GIFT strain of Nile tilapia was estimated in this study, using the broken-line model, between 0.75% and 0.80% of the diet (with a cysteine level of 0.50% of the diet), which is higher than 0.49% of the diet previously estimated for conventional Nile tilapia at the juvenile stage. Therefore, the genetic improvement applied to the GIFT strain of Nile tilapia likely led to a higher methionine and total sulfur amino acid requirement than the conventional strains. The results of this study support the need to update the existing nutrient requirement databases of fish, in order to ensure that diets are formulated to effectively satisfy the requirements of not only conventional, but also improved strains of fish, for the full expression of their accrued growth potential of the latter strains.

Optimal dietary methionine requirement of sub-adult turbot (Scophthalmus maximus L.): Growth performance, feed utilization and hepatic lipid metabolism

Optimal dietary methionine requirement of sub-adult turbot (Scophthalmus maximus L.): Growth performance, feed utilization and hepatic lipid metabolism

Dietary Methionine does not Reduce Penetrance in Curly Tail Mice but Causes a Phenotype-Specific Decrease in Embryonic Growth

The mouse mutation, curly tail, has incomplete penetrance and variable expression. Approximately 60% of the mice have a curly tail (CT), from which up to 20% may have lumbosacral spina bifida. Approximately 40% are normal, with a straight tail (ST). We tested whether L-methionine, which reduces the penetrance of neural tube defects in the Axd mouse mutant, has beneficial effects in the curly tail mutant. A single injection of L-methionine (200–1600 mg/kg body wt) on d 9 of pregnancy had no effect on the embryos, whereas there was a minor increase in penetrance at the highest dose. Chronic supplementation of L-methionine via the drinking water (1554 mg·kg body wt-1·d-1) did not shift penetrance. However, it decreased the weight of d 13 embryos from ST dams but not of those from CT dams. This phenotype-specific difference in response was evident and most unexpected. Mice from curly tail and other inbred strains were subjected to an L-methionine loading test and serum homocysteine assay. The different strains varied in their basal serum homocysteine concentrations, and they had proportionate significant increases after L-methionine loading. In CT and ST mice, basal serum homocysteine concentrations as well as the levels after loading were similar to each other and intermediate in the range of the mice tested. We conclude that L-methionine does not reduce penetrance in the curly tail mouse and that this strain reflects no derangement in L-methionine handling.

The effects of age, genotype and diet on hippocampal subfield iron dysregulation and Alzheimer's disease biomarkers in an ApoE mouse model.

Current theories regarding accumulation of Alzheimer's disease-related deposits of abnormal intra- and extracellular proteins include reactions to inflammation and mitochondrial dysfunction. In this study, we explored whether age, genotype and inflammation via diet have a greater effect on dysregulatory protein accumulation in any particular subfield of the hippocampus. We stained for ferritin, ferroportin, hyperphosphorylated tau and β-amyloid proteins in the hippocampal region of Apolipoprotein E2 (ApoE2), ApoE3 or ApoE4 mice fed a control diet or a hypothesized inflammation-inducing methionine diet and euthanized at 3, 6, 9 or 12 months. We analysed stains based on hippocampal subfield and compared the protein accumulation levels within each group. We found significantly decreased ferritin expression in ApoE4 mice in the CA1 and Hi regions and decreased ferroportin expression in ApoE4 mice in the Hi region. There was also a significant effect on hyperphosphorylated tau protein levels based upon a given mouse genotype and diet interaction. Additionally, there were nonsignificant trends in each hippocampal subfield of increasing ferroportin and hyperphosphorylated tau after 6months of age and decreasing β-amyloid and ferritin with age. This study identified that there are changes in iron regulatory molecules based on genotype in the Hi and CA1 regions. Our findings also suggest a diet-genotype interaction, which affects levels of specific Alzheimer's disease biomarkers in the hippocampus. Additionally, we identified a trend toward increased ability to clear β-amyloid and decreased ability to clear hyperphosphorylated tau with age in all subfields, in addition to evidence of increasing iron load with time.

In Vivo Methylation Capacity Is Not Impaired in Healthy Men during Short-Term Dietary Folate and Methyl Group Restriction

Ten healthy adult men were fed a diet low in folate and exogenous methyl groups to study the effects on in vivo methylation capability. The men were housed in a metabolic unit for the entire 108 d of the study. After a 9-d baseline period (Period 1), the men were fed a soy-product-amino acid defined diet for 45 d, which provided 25 µg/d of folate for 30 d (Period 2) and, with a folate supplement, 99 µg/d for 15 d (Period 3). During Period 2 and Period 3, the low methionine and choline diet was supplemented with methionine for half the subjects to vary the dietary methyl group intake. The periods were then repeated over the next 54 d (Periods 4–6), with a crossover of methionine intakes in Period 5 and Period 6. A 1-g oral dose of nicotinamide was given at the end of each period and methylated urine metabolites determined. Other measures related to in vivo methylation capability included urine creatinine, and plasma and urine carnitine. Even with moderate folate depletion, none of these measures was decreased by low methionine and choline intakes. Plasma methionine concentrations were unchanged throughout. Limiting exogenous methyl group intake by restricting dietary methionine and choline did not impair in vivo methylation capabilities for the variables tested, even at low folate intake.

Deoxyschizandrin ameliorates obesity and non-alcoholic fatty liver disease: Involvement of dual Farnesyl X receptor/G protein-coupled bile acid receptor 1 activation and leptin sensitization.

Natural dual farnesyl X receptor (FXR)/G protein-coupled bile acid receptor 1 (TGR5) activators have received little attention in the management of metabolic diseases. Deoxyschizandrin (DS), a natural lignan, occurs in S. chinensis fruit and has potent hepatoprotective effects, whereas its protective roles and mechanisms against obesity and non-alcoholic fatty liver disease (NAFLD) are largely elusive. Here, we identified DS as a dual FXR/TGR5 agonist using luciferase reporter and cyclic adenosine monophosphate(cAMP) assays. DS was orally or intracerebroventricularly administrated to high-fat diet-induced obesity (DIO) mice, and methionine and choline-deficient L-amino acid diet (MCD diet)-induced non-alcoholic steatohepatitis to evaluate its protective effects. Exogenous leptin treatment was employed to investigate the sensitization effect of DS on leptin. The molecular mechanism of DS was explored by Western blot, quantitative real-time PCR analysis, and ELISA. The results showed that DS activated FXR/TGR5 signaling and effectively reduced NAFLD in DIO and MCD diet-fed mice. DS countered obesity in DIO mice by promoting anorexia and energy expenditure and reversing leptin resistance, involving both peripheral and central TGR5 activation and leptin sensitization. Our findings indicate that DS may be a novel therapeutic approach for alleviating obesity and NAFLD through regulating FXR and TGR5 activities and leptin signaling.

Dietary methionine restriction attenuates cognitive dysfunction associated with sleep deprivation by promoting production of hydrogen sulfide, upregulating expression of BDNF and suppressing neuro-inflammation in rats

IntroductionIn this study, we aimed to study the potential role of H2S and the application of dietary methionine restriction (DMR) in the treatment of cognitive dysfunction in sleep deprived rat models.Material and methodsThe rat groups were established as a Control group, a sleep deprivation (SD) group, a SD + NaSH group and a SD + DMR group. Behavioral data was studied via Morris water maze test. TUNEL assay, real-time PCR, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were performed to study the differences of cognitive impairment related genes and proteins in different rat groups.ResultsPath length and escape latency were higher in the sleep deprived rats compared with the control rats, which were subsequently recovered by the treatment of NaSH or DMR. Also, DMR most significantly recovered the cognitive impairment and neuron status of sleep deprived rats compared with the administration of NaSH. The elevated level of hippocampal Iba1 and H2S production was recovered by NaSH and DMR, and the expressions of hippocampal phenotypic-related genes including NOS, CD68, CD32 and CD206 mRNA also showed similar trend as hippocampal Iba1. Meanwhile, the increased relative expression of IL-6 and IL-4 were recovered by DMR in sleep deprived rats, while the reduced level of hippocampal brain-derived neurotrophic factor (BDNF) and cystathionine γ-lyase (CSE) were elevated by the treatment of NaSH and MDR, with MDR exhibiting the most significant effect.ConclusionsThe application of DMR could attenuate cognitive dysfunction in sleep deprivation rats by upregulating the production of H2S and BDNF expression and alleviating neuro-inflammation responses.