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Proceedings of the National Academy of... Jul 2021Reports of biogenic methane (CH) synthesis associated with a range of organisms have steadily accumulated in the literature. This has not happened without controversy...
Reports of biogenic methane (CH) synthesis associated with a range of organisms have steadily accumulated in the literature. This has not happened without controversy and in most cases the process is poorly understood at the gene and enzyme levels. In marine and freshwater environments, CH supersaturation of oxic surface waters has been termed the "methane paradox" because biological CH synthesis is viewed to be a strictly anaerobic process carried out by O-sensitive methanogens. Interest in this phenomenon has surged within the past decade because of the importance of understanding sources and sinks of this potent greenhouse gas. In our work on Yellowstone Lake in Yellowstone National Park, we demonstrate microbiological conversion of methylamine to CH and isolate and characterize an sp. capable of this activity. Furthermore, we identify and clone a gene critical to this process (encodes pyridoxylamine phosphate-dependent aspartate aminotransferase) and demonstrate that this property can be transferred to with this gene and will occur as a purified enzyme. This previously unrecognized process sheds light on environmental cycling of CH, suggesting that O-insensitive, ecologically relevant aerobic CH synthesis is likely of widespread distribution in the environment and should be considered in CH modeling efforts.
Topics: Aerobiosis; Bacteria; Betaine; DNA Mutational Analysis; Methane; Microbiota; Mutation; Water
PubMed: 34183407
DOI: 10.1073/pnas.2019229118 -
Journal of Alzheimer's Disease : JAD 2023Microglia-driven neuroinflammation has been shown to be involved in the entire process of Alzheimer's disease (AD). Betaine is a natural product that exhibits...
BACKGROUND
Microglia-driven neuroinflammation has been shown to be involved in the entire process of Alzheimer's disease (AD). Betaine is a natural product that exhibits anti-inflammatory activity; however, the exact underlying molecular mechanisms are poorly understood.
OBJECTIVE
Our study focused on determining the effect of betaine against amyloid-β42 oligomer (AβO)-induced inflammation in microglial BV2 cells and investigating the underlying mechanism.
METHODS
AβO was used to establish an in vitro AD model using BV2 cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to measure BV2 cell viability with different concentrations of AβO and betaine. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the expression levels of inflammatory factors, such as interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor α (TNF-α). Western blotting was used to evaluate the activation of the NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome and nuclear transcription factor-κB p65 (NF-κB p65). Moreover, we used phorbol 12-myristate 13-acetate (PMA) to activate NF-κB in order to validate that betaine exerted anti-neuroinflammatory effects through regulation of the NF-κB/NLRP3 signaling pathway.
RESULTS
We used 2 mM betaine to treat 5μM AβO-induced microglial inflammation. The administration of betaine effectively decreased the levels of IL-1β, IL-18, and TNF-α without affecting cell viability in BV2 microglial cells.
CONCLUSION
Betaine inhibited AβO-induced neuroinflammation in microglia by inhibiting the activation of the NLRP3 inflammasome and NF-κB, which supports further evaluation of betaine as a potential effective modulator for AD.
Topics: Humans; NF-kappa B; Microglia; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Interleukin-18; Betaine; Neuroinflammatory Diseases; Tumor Necrosis Factor-alpha; Signal Transduction; Inflammation; Amyloid beta-Peptides
PubMed: 37334594
DOI: 10.3233/JAD-230064 -
Cellular Physiology and Biochemistry :... 2013Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more... (Review)
Review
Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress. This process has been studied in great detail. In liver, the main role of betaine is a methyl donor in the methionine cycle. However, recent studies showed that BGT1 is much more abundant in liver compared to kidney medulla. Despite this, the role of BGT1 in liver has received little attention. Entry of betaine into liver cells is a necessary first step for its action at the cellular level. Increased interest in betaine has developed because of a number of therapeutic uses. These include treatment of nonalcoholic fatty liver and hyperhomocysteinemia, a risk factor for atherosclerotic disease. Several important questions need to be addressed to better understand the potential of betaine as a therapeutic agent for other liver diseases, such as alcohol-induced injury. Heavy alcohol consumption is the most common cause for liver-related deaths and altered liver metabolism may contribute to hepatic, vascular, coronary, and cerebral diseases.
Topics: Alcohol Drinking; Betaine; Biological Transport; Carrier Proteins; GABA Plasma Membrane Transport Proteins; Hepatocytes; Humans; Kidney; Kidney Medulla; Liver
PubMed: 24429813
DOI: 10.1159/000356622 -
Biomedicine & Pharmacotherapy =... Jun 2022Betaine (N, N, N-trimethylglycine) is an amino-acid derivative exerting numerous beneficial effects on the organism. This compound is found in human and animal diets but... (Review)
Review
Betaine (N, N, N-trimethylglycine) is an amino-acid derivative exerting numerous beneficial effects on the organism. This compound is found in human and animal diets but is also endogenously generated. However, its synthesis may be insufficient to maintain or improve health. Moreover, the tissue content of betaine reduces under some pathological conditions, such as type 2 diabetes. This decrease may be, however, easily alleviated by dietary betaine supplementation. Rodent studies provided evidence that betaine effectively limits many diabetes-related disturbances. Betaine therapy improves glucose tolerance and insulin action, which is strongly associated with changes in insulin-sensitive tissues, such as skeletal muscle, adipose tissue, and liver. Betaine supplementation positively affects multiple genes, which expression is dysregulated in diabetes. AMP-activated protein kinase is thought to play a central role in the mechanism underlying the anti-diabetic betaine action. Moreover, studies with animal models of type 2 diabetes have shown that betaine exerts anti-inflammatory and anti-oxidant effects, and also alleviates endoplasmic reticulum stress. These changes contribute to improved insulin sensitivity and better blood glucose clearance. The results of animal studies encourage the exploration of the therapeutic betaine efficacy in humans with type 2 diabetes.
Topics: Animals; Betaine; Diabetes Mellitus, Type 2; Insulin; Insulin Resistance; Rodentia
PubMed: 35413601
DOI: 10.1016/j.biopha.2022.112946 -
The American Journal of Clinical... Oct 2021Sufficient choline and betaine during pregnancy are needed for fetal growth and development.
BACKGROUND
Sufficient choline and betaine during pregnancy are needed for fetal growth and development.
OBJECTIVES
We aimed to investigate the associations between maternal plasma choline and betaine in the third trimester of pregnancy and child growth from birth up to 8 years of age.
METHODS
Concentrations of choline and betaine were measured in plasma of 1331 pregnant women from the KOALA (Kind, Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg) Birth Cohort Study in the Netherlands. Child weight and height were measured at birth and at 1 (91% complete), 2 (86%), and 6-8 y (76%). Birth weight, weight gain in the first year, and z scores for weight and height at 1 and 2 y were used as continuous outcome variables. BMI z scores at 1 and 2 y were used as continuous and dichotomous outcomes, and BMI z scores at age 6-8 y were used to study overweight at that age.
RESULTS
Each 1-µmol/L increase of maternal plasma choline was associated with a mean 20-g (95% CI: 1.1, 38.0 g) higher weight gain in the first year of life, and a higher BMI z score (β: 0.02; 95% CI: 0.00, 0.04) and slightly higher odds of BMI z score >85th percentile (OR: 1.08; 95% CI: 1.03, 1.10) at 1-2 y. Each 1-µmol/L increase of plasma betaine was associated with a mean 12-g (95% CI: 0.8, 23.9 g) higher weight gain in the first year of life and higher odds of BMI z score >85th percentile at 1-2 y (OR: 1.03; 95% CI: 1.00, 1.07). Lastly, betaine was associated with overweight at 6-8 y (OR: 1.17; 95% CI: 1.02, 1.34), only in boys.
CONCLUSIONS
Third-trimester pregnancy plasma choline and betaine were positively associated with childhood anthropometric measures. In boys, some of the associations may have persisted up to 8 y of age. Further studies may investigate the validity of maternal plasma choline and betaine concentrations as markers of maternal intake and fetal transfer.
Topics: Adult; Betaine; Biomarkers; Child; Choline; Cohort Studies; Female; Humans; Male; Pregnancy; Prenatal Nutritional Physiological Phenomena
PubMed: 34113974
DOI: 10.1093/ajcn/nqab177 -
International Journal of Molecular... Oct 2022Abiotic stresses, such as drought, salinity, heat, cold, and heavy metals, are associated with global climate change and hamper plant growth and development, affecting... (Review)
Review
Abiotic stresses, such as drought, salinity, heat, cold, and heavy metals, are associated with global climate change and hamper plant growth and development, affecting crop yields and quality. However, the negative effects of abiotic stresses can be mitigated through exogenous treatments using small biomolecules. For example, the foliar application of melatonin provides the following: it protects the photosynthetic apparatus; it increases the antioxidant defenses, osmoprotectant, and soluble sugar levels; it prevents tissue damage and reduces electrolyte leakage; it improves reactive oxygen species (ROS) scavenging; and it increases biomass, maintains the redox and ion homeostasis, and improves gaseous exchange. Glutathione spray upregulates the glyoxalase system, reduces methylglyoxal (MG) toxicity and oxidative stress, decreases hydrogen peroxide and malondialdehyde accumulation, improves the defense mechanisms, tissue repairs, and nitrogen fixation, and upregulates the phytochelatins. The exogenous application of proline enhances growth and other physiological characteristics, upregulates osmoprotection, protects the integrity of the plasma lemma, reduces lipid peroxidation, increases photosynthetic pigments, phenolic acids, flavonoids, and amino acids, and enhances stress tolerance, carbon fixation, and leaf nitrogen content. The foliar application of glycine betaine improves growth, upregulates osmoprotection and osmoregulation, increases relative water content, net photosynthetic rate, and catalase activity, decreases photorespiration, ion leakage, and lipid peroxidation, protects the oxygen-evolving complex, and prevents chlorosis. Chemical priming has various important advantages over transgenic technology as it is typically more affordable for farmers and safe for plants, people, and animals, while being considered environmentally acceptable. Chemical priming helps to improve the quality and quantity of the yield. This review summarizes and discusses how exogenous melatonin, glutathione, proline, and glycine betaine can help crops combat abiotic stresses.
Topics: Melatonin; Betaine; Proline; Glutathione; Antioxidants; Stress, Physiological
PubMed: 36361700
DOI: 10.3390/ijms232112913 -
International Journal of Molecular... Jun 2022Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver, which is often associated with disrupted iron homeostasis. Betaine...
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver, which is often associated with disrupted iron homeostasis. Betaine has been reported to be hepatoprotective, yet whether and how betaine ameliorates high-fat diet-induced disruption of hepatic lipid and iron homeostasis remains elusive. In this study, mice were fed either standard (CON) or high-fat diet (HFD) for 9 weeks to establish a NAFLD model. Mice raised on HF diet were then assigned randomly to HF and HFB groups, HFB group being supplemented with 1% (/) of betaine in the drinking water for 13 weeks. Betaine supplementation significantly alleviated excessive hepatic lipid deposition and restored hepatic iron content. Betaine partly yet significantly reversed HFD-induced dysregulation of lipogenic genes such as PRARγ and CD36, as well as the iron-metabolic genes including FPN and HAMP that encodes hepcidin. Similar mitigation effects of betaine were observed for BMP2 and BMP6, the up-stream regulators of hepcidin expression. Betaine significantly rectified disrupted expression of methyl transfer gene, including BHMT, GNMT and DNMT1. Moreover, HFD-modified CpG methylation on the promoter of PRARγ and HAMP genes was significantly reversed by betaine supplementation. These results indicate that betaine alleviates HFD-induced disruption of hepatic lipid and iron metabolism, which is associated with modification of CpG methylation on promoter of lipogenic and iron-metabolic genes.
Topics: Animals; Betaine; Diet, High-Fat; Hepcidins; Homeostasis; Iron; Lipid Metabolism; Lipids; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease
PubMed: 35682942
DOI: 10.3390/ijms23116263 -
Nutrients Nov 2022The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate... (Randomized Controlled Trial)
Randomized Controlled Trial
The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1α Gene Expression.
The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate concentrations, and exercise-associated biomarkers. Eighteen recreationally trained males (25 ± 5 y) were randomized to supplement 6 g/day of either betaine anhydrous (BET) or cellulose placebo (PLA) for 14 days. Subsequently, subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs (BFR [LL-BFR; 20% 1RM at 80% arterial occlusion pressure] and high-load [HL; 70% 1RM]). Toe-tip lactate concentrations were sampled before (PRE), as well as immediately (POST0), 30 min (POST30M), and 3 h (POST3H) post-exercise. Serum homocysteine (HCY), growth hormone (GH) and insulin-like growth factor-1 concentrations were additionally assessed at PRE and POST30M. Analysis failed to detect any significant between-supplement differences for total repetitions completed. Baseline lactate changes (∆) were significantly elevated from POST0 to POST30 and from POST30 to POST3H (p < 0.05), whereby HL additionally demonstrated significantly higher ∆Lactate versus LL-BFR (p < 0.001) at POST3H. Although serum ∆GH was not significantly impacted by supplement or condition, serum ∆IGF-1 was significantly (p = 0.042) higher in BET versus PLA and serum ∆HCY was greater in HL relative to LL-BFR (p = 0.044). Although these data fail to support a BFR-betaine synergy, they otherwise support betaine’s anabolic potential.
Topics: Humans; Male; Betaine; Biomarkers; Blood Flow Restriction Therapy; Gene Expression; Hypoxia-Inducible Factor 1, alpha Subunit; Lactic Acid; Muscle, Skeletal; Regional Blood Flow; Resistance Training; Young Adult; Adult
PubMed: 36501070
DOI: 10.3390/nu14235040 -
Environmental Microbiology May 2022Glycine betaine (GBT) is a compatible solute in high concentrations in marine microorganisms. As a component of labile organic matter, GBT has complex biochemical...
Glycine betaine (GBT) is a compatible solute in high concentrations in marine microorganisms. As a component of labile organic matter, GBT has complex biochemical potential as a substrate for microbial use that is unconstrained in the environment. Here we determine the uptake kinetics and metabolic fate of GBT in two natural microbial communities in the North Pacific characterized by different nitrate concentrations. Dissolved GBT had maximum uptake rates of 0.36 and 0.56 nM h with half-saturation constants of 79 and 11 nM in the high nitrate and low nitrate stations respectively. During multiday incubations, most GBT taken into cells was retained as a compatible solute. Stable isotopes derived from the added GBT were also observed in other metabolites, including choline, carnitine and sarcosine, suggesting that GBT was used for biosynthesis and for catabolism to pyruvate and ammonium. Where nitrate was scarce, GBT was primarily metabolized via demethylation to glycine. Gene transcript data were consistent with SAR11 using GBT as a source of methyl groups to fuel the methionine cycle. Where nitrate concentrations were higher, more GBT was partitioned for lipid biosynthesis by both bacteria and eukaryotic phytoplankton. Our data highlight unexpected metabolic pathways and potential routes of microbial metabolite exchange.
Topics: Betaine; Biological Transport; Choline; Microbiota; Nitrates
PubMed: 35466501
DOI: 10.1111/1462-2920.16020 -
Nutrients Sep 2020Betaine has been demonstrated to increase tolerance to hypertonic and thermal stressors. At the cellular level, intracellular betaine functions similar to molecular... (Review)
Review
Betaine has been demonstrated to increase tolerance to hypertonic and thermal stressors. At the cellular level, intracellular betaine functions similar to molecular chaperones, thereby reducing the need for inducible heat shock protein expression. In addition to stabilizing protein conformations, betaine has been demonstrated to reduce oxidative damage. For the enterocyte, during periods of reduced perfusion as well as greater oxidative, thermal, and hypertonic stress (i.e., prolonged exercise in hot-humid conditions), betaine results in greater villi length and evidence for greater membrane integrity. Collectively, this reduces exercise-induced gut permeability, protecting against bacterial translocation and endotoxemia. At the systemic level, chronic betaine intake has been shown to reduce core temperature, all-cause mortality, markers of inflammation, and change blood chemistry in several animal models when exposed to heat stress. Despite convincing research in cell culture and animal models, only one published study exists exploring betaine's thermoregulatory function in humans. If the same premise holds true for humans, chronic betaine consumption may increase heat tolerance and provide another avenue of supplementation for those who find that heat stress is a major factor in their work, or training for exercise and sport. Yet, this remains speculative until data demonstrate such effects in humans.
Topics: Animals; Betaine; Body Temperature Regulation; Carbohydrates; Caseins; Dietary Supplements; Endotoxemia; Heat-Shock Proteins; Heat-Shock Response; Hot Temperature; Humans; Lipids; Lipopolysaccharides; Molecular Chaperones; Osmotic Pressure; Plant Proteins, Dietary; Thermotolerance
PubMed: 32992781
DOI: 10.3390/nu12102939