The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.

We have reported that D,L-thiol esters, including D-cysteine ethyl ester (D-CYSee), are effective at overcoming opioid-induced respiratory depression (OIRD) in rats. Our on-going studies reveal that co-injections of D-CYSee with multi-day morphine injections markedly diminish spontaneous withdrawal that usually occurs after cessation of multiple injections of morphine in rats. Chronically administered opioids are known (1) to alter cellular redox status, thus inducing an oxidative state, and (2) for an overall decrease in DNA methylation, therefore resulting in the transcriptional activation of previously silenced long interspersed elements (LINE-1) retrotransposon genes. The first objective of the present study was to determine whether D-CYSee and the one carbon metabolism with the methyl donor, betaine, would maintain redox control and normal DNA methylation levels in human neuroblastoma cell cultures (SH-SY5Y) under overnight challenge with morphine (100 nM). The second objective was to determine whether D-CYSee and/or betaine could diminish the degree of physical dependence to morphine in male Sprague Dawley rats. Our data showed that overnight treatment with morphine reduced cellular GSH levels, induced mitochondrial damage, decreased global DNA methylation, and increased LINE-1 mRNA expression. These adverse effects by morphine, which diminished the reducing capacity and compromised the maintenance of the membrane potential of SH-SY5Y cells, was prevented by concurrent application of D-CYSee (100 µM) or betaine (300 µM). Furthermore, our data demonstrated that co-injections of D-CYSee (250 µmol/kg, IV) and to a lesser extent, betaine (250 µmol/kg, IV), markedly diminished the development of physical dependence induced by multi-day morphine injections (escalating daily doses of 10-30 mg/kg, IV), as assessed by the lesser number of withdrawal phenomena elicited by the injection of the opioid receptor antagonist, naloxone (1.5 mg/kg, IV). These findings provide evidence that D-CYSee and betaine prevent the appearance of redox alterations and epigenetic signatures commonly seen in neural cells involved in opioid physical dependence/addiction, and lessen development of physical dependence to morphine.

The Use of Polyhexanide and Betaine Combined Preparation in Adult Burn Care in Sri Lanka.

Biofilm formation over burn wounds has led to persistent wound infection, poor wound healing, and resistance to antimicrobial therapy. This process ultimately leads to prolonged hospital stays and increased cost of burn wound care, especially in developing countries. Hence, large-area biofilm-targeted therapy should be a mainstay in burn wound care. Polyhexanide is a polymer used as a disinfectant, and betaine is a surfactant. We report a patient managed with a combined preparation of the above two substances. A 44-year-old patient sustained a 22% superficial partial-thickness and mid-dermal burns on the back and right arm after a high-voltage electrocution injury. The patient was treated with dressings containing the above preparation and closely monitored for the healing stages of the burn wound. Complete wound epithelialization with healthy granulation tissue was achieved within 15 days. No surface wound swab culture became positive during the treatment. The patient did not develop any fever spikes, and the white blood cell count was maintained at less than 12,000 mm-3 with a C-reactive protein level below 50 mg/L. No surgical intervention was needed for further management of the wound. Polyhexanide and betaine combined preparation may be used effectively on the superficial partial-thickness and mid-dermal burns to prevent wound infection and improve granulation and epithelialization. However, high-quality comparative evidence is needed for the confirmation.

Lipidomics analysis of microalgal lipid production and heavy metal adsorption under glycine betaine-mediated alleviation of low-temperature stress.

Heavy metal pollution in the cold region is serious, affecting human health and aquatic ecology. This study investigated the ability of microalgae to remove heavy metals (HMs) and produce lipid at low temperature. The removal efficiency of different HMs (Cd2+, Cu2+, Cr3+ and Pb2+), cell growth and lipid synthesis of microalgae were analyzed at 15 °C. Moreover, addition of glycine betaine (GB) further enhanced the productivity of microalgae in treating HMs and lipid production, and simultaneously increased the antioxidant capacity of microalgae against environmental stresses. The results showed that the highest lipid productivity of 100.98 mg L-1 d-1 and the removal efficiency of 85.8 % were obtained under GB coupled with Cr3+. The highest glutathione content of 670.34 nmol g-1 fresh alga was achieved under GB coupled with Pb2+. In addition, lipidomics showed that GB was able to up-regulate the triglyceride and diglyceride content, influenced fatty acid composition to regulate the microalgal metabolism, and mediated lipid accumulation under 15 °C mainly through the regulation of glycerol ester metabolism. This study provided a new perspective on microalgal lipid production and the removal of HMs in cold regions and provided evidence for the use of phytohormones to improve the algal environmental resistance.

Zwitterionic Amino-Acid-Derived Polyacrylamides with a Betaine Twist - Synthesis and Characterization.

Amino-acid-derived polyzwitterions and polybetaines (PBs) are two promising alternatives to non-ionic polymers, for example, to increase tumor permeability. In this study, amino-acid-derived polyzwitterions are synthesized and a strategy to quarternize the amine in the side chain functional group is developed to combine the advantages of both types. The functional monomer is polymerized via reversible addition-fragmentation chain-transfer polymerization for which a kinetic study is performed. Further, the impact of the permanent positive charge on amino-acid-derived polyzwitterions is studied based on two zwitterionic polymers obtained via post-polymerization modification (PPM) of Poly(N-acryloxysuccinimide) to allow good comparison between methylated and non-methylated polymers. Circular dichroism shows that the stereocenter remains intact during PPM. pH titration and ζ-potential measurements show that the methylated polymer has a negative ζ-potential over the measured pH range and, therefore, the polymer remains zwitterionic over a broader pH range than its non-methylated equivalent. Both polymers are well tolerated by mammalian cells up to concentrations of 1 mg mL-1. The study introduces a path to a new polymer class that combines the advantages of both PBs and amino-acid-derived polyzwitterions and highlights the impact a permanent charge has on the physiochemical properties.

Prophylactic Effects of Betaine on Depression and Anxiety Behaviors in Mice with Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis (UC) is a typical type of inflammatory bowl disease, which is accompanied by an increased risk of depression and anxiety-related psychological symptoms. Betaine is a naturally derived compound that can function as an anti-inflammatory drug and a neuromodulator. In-depth exploration of the potential role of betaine in treating UC-related depression and anxiety is crucial. This study aimed to elucidate the effects of betaine on UC-related depression and anxiety and clarify the underlying mechanisms. A dextran sulfate sodium (DSS)-induced mice model was established by 4% DSS drinking ad libitum for 7 days. The colonic injury was measured using hematoxylin-eosin (HE) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining. Depression and anxiety-like behaviors were separately evaluated using a forced swimming test (FST), a tail suspension test (TST), a light-dark box test (LDBT), and an open field test (OFT). Immunohistochemistry was used to detect DNA damage and neurogenesis in the hippocampus. Western blotting was applied to detect the protein levels of macrophage polarization in mice colons and the alteration of mitochondrial dysfunction and the cGAS-STING pathway in the hippocampus. Betaine strongly alleviated mucosal structural disorder and mucin secretion reduction and promoted M2-macrophage polarization in the colon of DSS-treated mice. In addition, betaine could mitigate depression- and anxiety-like behaviors in DSS-treated mice, reduce the DNA damage and mitochondrial dysfunction, and inhibit the cGAS-STING signaling pathway. Our study reveals the antidepression/anxiety effects of betaine and further demonstrates the potential mechanism by which betaine inhibits DNA damage and mitochondrial dysfunction to block the cGAS-STING pathway, thereby repairing neurogenesis in the hippocampus.

Preparation and evaluation of a pyridine sulfonate betaine-based zwitterionic stationary phase for hydrophilic interaction chromatography.

A zwitterionic stationary phase comprising pyridinium cations and sulfonate anions was successfully developed through thiol-ene click chemistry. Using seven polar small molecules as probes, the zwitterionic stationary phase showed high separation selectivity and excellent column efficiency (35,200-54,800 plates/m) compared with two commercial columns. The influence of water proportion, salt concentration, and pH in the mobile phase, and column temperature, on the retention of six polar compounds was examined. The retention mechanism was explored by three hydrophilic retention models, Tanaka test and linear solvation energy relationship analysis. For the analysis of sample dairy products (milk powder, milk, and yogurt), the stationary phase was operated in hydrophilic interaction chromatography mode without the addition of buffer salts, facilitating rapid and efficient detection and quantification of melamine. The LOD and LOQ are 0.04 mg⋅g-1 and 0.13 mg⋅g-1, respectively, and the recovery rate is 90.3 - 102.8 %. The zwitterionic stationary phase has the advantages of simple preparation, good method reproducibility, good selectivity and high precision.

Betaine Suppresses Lipid Accumulation in Liver: Inhibition of FoxO6 and PPARγ Interaction.

Betaine is the major water-soluble component of Lycium chinensis. Although there are reports of a protective effect of betaine on fatty liver disease, the underlying mechanisms are unclear. We attempted to elucidate the molecular regulation of betaine on hyperglycemia-induced hepatic lipid accumulation via Forkhead box O (FoxO)6 activation. HepG2 cells and liver tissue isolated from db/db mice treated with betaine were used. The present study investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO6/peroxisome proliferator-activated receptor gamma (PPARγ) signaling in liver cells. Interestingly, betaine notably decreased lipid accumulation in tissues with FoxO6-induced mRNA expression of lipogenesis-related genes. Furthermore, betaine inhibited the FoxO6 interaction with PPARγ and cellular triglycerides in high-glucose- or FoxO6-overexpression-treated liver cells. In addition, we confirmed that betaine administration via oral gavage significantly ameliorated hepatic steatosis in db/db mice. We conclude that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the interaction between FoxO6 and PPARγ, thereby suppressing lipogenic gene transcription.

Investigation of biodegradable surfactant as a corrosion inhibitor to the cold rolled steel in the membrane separation device process.

The membrane process is an effective way to realize resource reutilization. Most membrane devices are made of cold-roll steel (CRS), which is easy to corrode when operating in acid conditions. Herein, the biodegradable surfactant dodecyl dimethyl betaine (BS-12) was used as the inhibitor to protect the CRS in the trichloroacetic acid (TCA) solution. The long-term stability membrane tests showed that adding BS-12 will not harm the membrane performance. The weight loss experiments proved that adding BS-12 with trace amount (10 mg·L-1) endowed the CRS with good inhibition efficiency (95.3 %). The electrochemical tests indicated that the mixed inhibitor- BS-12 works by inhibiting the anode and cathode simultaneously, and the polarization resistance increased to 21 times. The SEM, AFM, and CLSM tests proved that adding BS-12 enabled the CRS surface to remain stable. The FTIR and XPS tests proved that BS-12 adsorbed on the CRS surface via physical and chemical adsorption. The theoretical calculations proved the horizontal adsorption of BS-12 on the CRS surface and the existence of the electron transfer within the BS-12 and CRS. The BS-12 showed great potential in the CRS inhibition of the membrane separation and purification processing.

Decoding betaine: A critical analysis of therapeutic potential vs. marketing hype - a narrative review.

Research interest in betaine supplementation has surged in recent years, for both enhancing sports performance and treating metabolic conditions. This surge aligns with an expanding market for betaine supplements, which are often marketed as promising aids for a range of metabolic conditions. Despite numerous in vitro and in vivo studies elucidating betaine's involvement in crucial metabolic pathways, consensus remains elusive on its clinical efficacy as a dietary supplement, based on results from randomized controlled trials. One analysis of dietary betaine intake in 28 observational studies showed a mean intake of 182 mg/day of betaine, with the main sources including grain-based foods, baked products, grains, cereals, and vegetables. Analysis of the results from human randomized clinical trials has shown that betaine supplementation improves body composition when combined with physical activity. Additionally, betaine supplementation decreases serum homocysteine (Hcy) levels, but does not affect liver enzymes, triglycerides (TG), or high-density lipoprotein (HDL) cholesterol levels, though it does increase total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels at doses ≥ 4 g/day. Market analysis has demonstrated that betaine is a popular supplement for supporting various physiological processes, such as digestibility, methylation, physical performance, and liver or cardiovascular health. Manufacturers suggest a diverse range of applications for betaine supplements, with fourteen different uses identified. Additionally, high variability can be seen in the recommended usage directions for betaine. This narrative research sheds light on the evolving landscape of betaine supplementation and highlights the need for further investigation to clarify its clinical efficacy.

Maternal Supplementation with Dietary Betaine during Late Gestation Increased Ewe Plasma Creatine and Lamb Thermoregulation under Field Conditions.

Twin lamb mortality is a significant economic problem impacting the Australian sheep industry. Maternal betaine supplementation improved lamb vigour and early post-natal survival when ewes and lambs were housed indoors, suggesting that betaine may be beneficial to feed under extensive pasture systems. This study investigated whether maternal betaine supplementation during late gestation would improve Merino twin lamb live weight, thermoregulation, vigour and survival to weaning under field conditions. Ewes received dietary betaine at either 0 g/day (CTL; n = 115) or 4 g/day from day 110 of gestation (dG 110) until ~49 days post-partum (pp) (BET; n = 115). Measures indicative of lamb viability and survival were collected within 4-24 h of birth and at ~49 days pp and ~93 days pp. BET ewes had higher creatine and creatinine concentrations at dG 130 than CTL ewes (p < 0.05). BET lambs had a higher rectal temperature within 4-24 h following birth than CTL lambs (p < 0.05). CTL lambs were heavier at ~49 days pp and grew faster from birth to ~49 days pp than BET lambs (both p < 0.05). The time taken after release from the researcher to first suckling was quicker in the CTL lambs than BET lambs (p < 0.05). This study demonstrated that supplementing betaine increased creatine concentration in twin-bearing ewes and thermoregulatory capacity in neonatal lambs under extensive grazing systems.

Betaine alleviates cerebellar endoplasmic reticulum stress and oxidative imbalance in a cuprizone model of multiple sclerosis in rat.

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system, especially the cerebellum, with numerous physical and mental symptoms. Oxidative stress caused by inflammation can play a role in the occurrence of this disease. Betaine, a natural methyl donor compound, has potent neuroprotective effects. Here, we investigated the effects of betaine on motor behavior, cerebellar histological changes, oxidative stress response, and endoplasmic reticulum stress in a cuprizone (CPZ)-induced multiple sclerosis model in male rats. Twenty Wistar adult male rats were randomly divided into four groups including control, MS, betaine-treated MS, and betaine groups. MS was induced by feeding animals with rodent chow containing 0.5% CPZ for 12 weeks. Betaine was daily administrated as 1% in drinking water for the last 6 weeks. The motor behavioral performance was evaluated by open field, rotarod, and reverse basket tests. Histological analysis of the cerebellum was performed by hematoxylin and eosin (H&E) and Cresyl violet (Nissl) staining. Oxidative stress factors (GSH, GSSG, GPX, GR, and GT) were assessed in the experimental groups and finally, the expression of ERS-associated proteins was measured using western blot analysis. Data showed that treatment with betaine could effectively prevent and reverse the adverse behavioral manifestation compared with the MS group. Betaine treatment protected cerebellar demyelination and neuron and Purkinje cell degeneration against CPZ-induced demyelination. Betaine attenuated the protein levels of ESR-related proteins in the cerebellum of MS rats and similarly increased the level of enzymes related to antioxidants in the cerebellum. Therefore, our results suggest that oral administration of betaine may be used as a novel adjunct therapy against cerebellar dysfunctions in an animal model of MS.

Integrated ultrasensitive metabolomics and single-cell transcriptomics identify crucial regulators of sheep oocyte maturation and early embryo development in vitro.

INTRODUCTION: Developmental competence of oocytes matured in vitro is limited due to a lack of complete understanding of metabolism and metabolic gene expression during oocyte maturation and embryo development. Conventional metabolic analysis requires a large number of samples and is not efficiently applicable in oocytes and early embryos, thereby posing challenges in identifying key metabolites and regulating their in vitro culture system. OBJECTIVES: To enhance the developmental competence of sheep oocytes, this study aimed to identify and supplement essential metabolites that were deficient in the culture systems. METHODS: The metabolic characteristics of oocytes and embryos were determined using ultrasensitive metabolomics analysis on trace samples and single-cell RNA-seq. By conducting integrated analyses of metabolites in cells (oocytes and embryos) and their developmental microenvironment (follicular fluid, oviductal fluid, and in vitro culture systems), we identified key missing metabolites in the in vitro culture systems. In order to assess the impact of these key missing metabolites on oocyte development competence, we performed in vitro culture experiments. Furthermore, omics analyses were employed to elucidate the underlying mechanisms. RESULTS: Our findings demonstrated that betaine, carnitine and creatine were the key missing metabolites in vitro culture systems and supplementation of betaine and L-carnitine significantly improved the blastocyst formation rate (67.48% and 48.61%). Through in vitro culture experiments and omics analyses, we have discovered that L-carnitine had the potential to promote fatty acid oxidation, reduce lipid content and lipid peroxidation level, and regulate spindle morphological grade through fatty acid degradation pathway. Additionally, betaine may participate in methylation modification and osmotic pressure regulation, thereby potentially improving oocyte maturation and early embryo development in sheep. CONCLUSION: Together, these analyses identified key metabolites that promote ovine oocyte maturation and early embryo development, while also providing a new viewpoint to improve clinical applications such as oocyte maturation or embryo culture.

In ovo betaine injection improves breast muscle growth in newly hatched goslings through FXR/IGF-2 pathway.

Betaine has been shown to enhance growth performance and increase breast muscle yield in ducks and broilers through various mechanisms, including the modification of DNA methylation. However, the impact of in ovo betaine injection on muscle growth in newly hatched goslings remains unclear. In this study, fifty eggs were injected with saline or betaine at 7.5 mg/egg prior to incubation, and the subsequent effects on breast muscle growth in the newly hatched goslings were investigated. Betaine significantly increased (P < 0.05) the hatch weight, breast muscle weight, and breast muscle index, accompanied by an augmentation in muscle bundle cross-sectional area. Concurrently, betaine significantly upregulated (P < 0.05) the expression levels of myogenic regulatory factors, including myogenin (MyoG) and paired box 7 (Pax7) both mRNA and protein, while downregulating (P < 0.05) the mRNA and protein levels of myostatin (MSTN). Histological analysis revealed a higher abundance of proliferating cell nuclear antigen (PCNA) and Pax7 immune-positive cells in the breast muscle of the betaine group, consistent with elevated PCNA and Pax7 mRNA and protein levels. Additionally, significantly increased (P < 0.05) contents of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) were observed in the breast muscle of the betaine group, so was mRNA expression of IGF-1, IGF-2, and insulin-like growth factor 1 receptor (IGF-1R). Betaine also significantly in8creased (P < 0.05) global DNA methylation of the breast muscle, accompanied by enhanced mRNA and protein levels of methionine cycle and DNA methylation-related enzymes, Interestingly, the promoter regions of IGF-1, IGF-2, and IGF-1R genes were significantly hypomethylated (P < 0.05). Moreover, in ovo betaine injection significantly upregulated (P < 0.05) the protein level of farnesoid X receptor (FXR) in breast muscle and FXR binding to the promoter of IGF-2 gene. These findings suggest that in ovo betaine injection promotes breast muscle growth during embryonic development in goslings through the FXR-mediated IGF-2 pathway, ultimately improving hatch weight and breast muscle weight.

Betaine and feed restriction as potential mitigation strategies against heat stress in two strains of laying hens.

Climate change is increasingly manifesting in temperate regions. Laying hens are highly sensitive to heat stress and mitigation strategies should be implemented to reduce the negative effects. The goal of this experiment was to evaluate the effects of betaine in drinking water (0.55 g/L) and 4 h feed restriction during peak heat stress on laying performance, egg quality, blood gas parameters, body temperature (Tb), and oxidative stress in 2 different breeds of laying hens. Therefore, 448 ISA Brown hens (25 wk) and 448 Lohmann LSL classic laying hens (26 wk) were housed in 128 cages (7 hens/cage). Thermoneutral (TN) data was collected for 21 d before cyclic heat stress (HS) (21d; 32 ± 2°C; 6 h daily). During HS, hens were divided into 4 treatments: 1) feed restriction (FR), 2) betaine supplementation in drinking water (BET), 3) feed restriction and betaine supplementation in drinking water (FR-BET), or 4) control (CON). The effects were evaluated after 1 wk of HS (acute heat stress; AHS) and 3 wk of HS (chronic heat stress; CHS). Laying rate and egg mass (EM) diminished during CHS but decreased more in white than brown hens (2.78% and 1.94%; -1.57% and -0.81%, respectively; P = 0.004) and remained unaltered by BET or FR. During AHS, average daily feed intake (ADFI) increased compared to TN, but the increase was higher in white than brown hens (6.36% and 2.62%, respectively; P = 0.001). Egg shell quality deteriorated during AHS and CHS, but was most affected in white hens, FR or BET did not impact this. Blood pCO2, HCO3- and base excess significantly decreased during AHS and CHS, but pH and iCa were unaltered. Blood glucose increased in white hens during AHS compared to TN (P < 0.001), while plasma malondialdehyde increased in brown hens (P < 0.001). Results indicated that laying hens experienced HS, but breed differences were observed and white hens were generally most affected. FR affected feed conversion ratio negatively during CHS. However, FR and BET could not improve laying performance, egg quality, Tb, or blood parameters during HS.

Molecular identification of haemoparasites in animals using blood lysate PCR: a quick and inexpensive alternative to purified whole genomic DNA.

Haemoparasitic diseases constitute a significant constraint to economic livestock farming. Diagnostic techniques that are inexpensive, rapid, reliable, and precise are crucial for the management of diseases. In this context, PCR assays are very valuable yet expensive since the samples must be processed before being included in the PCR reaction. Accordingly, the goal of the current study was to lower the PCR costs without jeopardizing the assay's sensitivity and specificity. For that purpose, the alkaline solution was optimized for low cost and quick DNA extraction (blood lysate), and PCR reagents were modified for optimum reaction. In comparison to purified whole blood genomic DNA, the currently developed and optimized blood lysate method was found to be 95.5% less expensive, as well as being equally sensitive and specific for the molecular detection (PCR) of haemoparasites like Babesia, Theileria, Trypanosoma and rickettsiales in cattle, buffaloes, horses, and dogs. The assay was also demonstrated to be quick, less likely to cross-contaminate, and appropriate for use in laboratories with limited resources. Therefore, the currently developed and optimized blood lysate method could serve as a viable alternative to purified whole blood genomic DNA for molecular detection (PCR) of haemoparasites in animals particularly in resource-limited settings.

[A soap to fight schistosomiasis: a field intervention worth considering?] / Un savon pour lutter contre les schistosomoses : une intervention de terrain à reprendre ?

An experiment was carried out in 1985-87 against schistosomiasis using products neutralizing the intermediate stages of schistosomes. In the laboratory, it had been shown that lauryl betaines, amphoteric substances, used for children's shampoos, quickly immobilized miracidiums and cercariae. Studies in Niger in field conditions with water laden with organic matter gave similar results. This surfactant can be incorporated into ordinary soaps at a dose of 5% without changing their characteristics. Betaine soaps were put on sale in ordinary commercial channels in Niger then in Côte d'Ivoire, in hyperendemic villages for Schistosoma haematobium. Betaines diffused without external intervention into the water used by populations for washing. The soaps were well accepted by these populations. However, after one year, the results in tested villages compared to control ones were unclear on the dynamics of urinary schistosomiasis in terms of prevalence and oviuria. Anti-schistosome treatment seems necessary at the start of the procedure. The use of soap by populations needed to be measured. In conclusion, this promising laboratory action deserves to be evaluated again in the field, in addition to health education and systematic treatment actions.

Betaine for the prevention and treatment of insulin resistance and fatty liver in a high-fat dietary model of insulin resistance in C57BL mice.

Aim: The aim was to investigate mechanisms by which betaine improves hepatic insulin signaling in a dietary mouse model of insulin resistance and fatty liver. Methods: C57BL 6J mice were fed a standard diet (SF), a standard diet with betaine (SFB), a nutritionally complete high fat (HF) diet, or a high fat diet with betaine (HFB) for 14 weeks. In a separate experiment, mice were fed high fat diet for 18 weeks, half of whom received betaine for the final 4 weeks. Activation of insulin signaling in the liver was assessed by western blot. Insulin signaling was also assessed in insulin resistant primary human hepatocytes treated with betaine. Results: As compared with SF, mice receiving HF diet were heavier, had more hepatic steatosis, and abnormal glucose tolerance test (GTT). Betaine content in liver and serum was 50% lower in HF than in SF; betaine supplementation restored serum and liver betaine content. Betaine treatment of HF reduced whole body insulin resistance as measured by GTT. Betaine treatment of HF increased tyrosine phosphorylation of insulin receptor substrate-1 and phosphorylation (activation) of Akt, and increased hepatic glycogen content. In vitro, betaine reversed insulin resistance in primary human hepatocytes by increasing insulin-stimulated tyrosine phosphorylation of IRS1 and of Akt. Conclusion: Betaine supplementation reduced whole body insulin resistance and increased activation of insulin signaling pathways in the liver in a mouse model of insulin resistance and fatty liver created by feeding a nutritionally complete high fat diet for 14 weeks. Betaine also reduced liver injury as assessed by ALT and by liver histology. In vitro, betaine reversed insulin resistance by increasing insulin-stimulated tyrosine phosphorylation of IRS1 and activation of downstream proteins in the insulin signaling cascade in insulin resistant primary human hepatocytes.

The Solvatomagnetism of ET(33) Betaine and of Its Phenolic Precursor.

The 1H and 13C NMR spectra of the N-(3,5-dichloro-4-hydroxyphenyl)- 2,4,6-triphenylpyridinium perchlorate and of its deprotonated betaine 4-(2,4,6-triphenylpyridinio)-2,6-dichlorophenolate (Wolfbeis's ET(33) dye) were recorded in various solvents and analyzed in search of solvent-dependent shifts that characterize their solvatomagnetism, which was compared with the well-known UV-vis spectral behavior of this important solvatochromic dye. Although the NMR spectra of ET(33) and its phenolic precursor in different solvents correlated only poorly with their UV-vis spectral responses, they provided valuable information on specific structural features and solute-solvent interactions that are not available from their UV-vis spectra.

Enhancing osmotic stress tolerance of cell mimetics by modulating lipid bilayer.

Seeking effective ways to maintain cellular homeostasis is crucial to the survival of organisms when they encounter osmotic stress. Glycine betaine (GB) is a widely generated natural osmolyte, but its endogenous production and action are limited. Herein, a kind of nonionic surfactant dodecyl-ß-d-glucopyranoside (DG) and a common polymer polyethylene glycol (PEG) are proven to have the ability to enhance the osmotic stress (induced by sugar concentration changes) tolerance of cell and organism models, those are giant unilamellar vesicles (GUVs) and gram-negative Escherichia coli. DG or PEG only induces small size decrease and certain shape change of GUVs. Importantly, DG or PEG at the concentration 100 times lower than that of GB effectively increases the survival rate of bacteria under both hypoosmotic and hyperosmotic conditions. This intriguing result is attributed to the insertion of DG or adsorption of PEG in the lipid bilayer membrane, leading to enhanced membrane permeability. These exogenous substances can replace GB to facilely and highly efficiently augment adaptation of organisms to osmotic stress.

Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1.

BACKGROUND: Mitochondrial dysfunction is one of the hallmarks of aging and a leading contributor to sarcopenia. Nutrients are essential for improving mitochondrial function and skeletal muscle health during the aging process. Betaine is a nutrient with potential muscle-preserving properties. However, whether and how betaine could regulate the mitochondria function in aging muscle are poorly understood. We aimed to explore the molecular target and underlying mechanism of betaine in attenuating the age-related mitochondrial dysfunction in skeletal muscle. METHODS: Young mice (YOU, 2 months), old mice (OLD, 15 months), and old mice with betaine treatment (BET, 15 months) were fed for 12 weeks. The effects of betaine on muscle mass, strength, function, and subcellular structure of muscle fibres were assessed. RNA sequencing (RNA-seq) was conducted to identify the molecular target of betaine. The impacts of betaine on mitochondrial-related molecules, superoxide accumulation, and oxidative respiration were examined using western blotting (WB), immunofluorescence (IF) and seahorse assay. The underlying mechanism of betaine regulation on the molecular target to maintain mitochondrial function was investigated by luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay. Adenoassociated virus transfection, succinate dehydrogenase staining (SDH), and energy expenditure assessment were performed on 20-month-old mice for validating the mechanism in vivo. RESULTS: Betaine intervention demonstrated anti-aging effects on the muscle mass (P = 0.017), strength (P = 0.010), and running distance (P = 0.013). Mitochondrial-related markers (ATP5a, Sdha, and Uqcrc2) were 1.1- to 1.5-fold higher in BET than OLD (all P ≤ 0.036) with less wasted mitochondrial vacuoles accumulating in sarcomere. Bioinformatic analysis from RNA-seq displayed pathways related to mitochondrial respiration activity was higher enriched in BET group (NES = -0.87, FDR = 0.10). The quantitative real time PCR (qRT-PCR) revealed betaine significantly reduced the expression of a novel mitochondrial regulator, Mss51 (-24.9%, P = 0.002). In C2C12 cells, betaine restored the Mss51-mediated suppression in mitochondrial respiration proteins (all P ≤ 0.041), attenuated oxygen consumption impairment, and superoxide accumulation (by 20.7%, P = 0.001). Mechanically, betaine attenuated aging-induced repression in Yy1 mRNA expression (BET vs. OLD: 2.06 vs. 1.02, P = 0.009). Yy1 transcriptionally suppressed Mss51 mRNA expression both in vitro and in vivo. This contributed to the preservation of mitochondrial respiration, improvement for energy expenditure (P = 0.008), and delay of muscle loss during aging process. CONCLUSIONS: Altogether, betaine transcriptionally represses Mss51 via Yy1, improving age-related mitochondrial respiration in skeletal muscle. These findings suggest betaine holds promise as a dietary supplement to delay skeletal muscle degeneration and improve age-related mitochondrial diseases.