Characterization of a Potential Probiotic Lactiplantibacillus plantarum LRCC5310 by Comparative Genomic Analysis and its Vitamin B6 Production Ability.

Safety assessment and functional analysis of probiotic candidates are important for their industrial applications. Lactiplantibacillus plantarum is one of the most widely recognized probiotic strains. In this study we aimed to determine the functional genes of L. plantarum LRCC5310, isolated from kimchi, using next-generation, whole-genome sequencing analysis. Genes were annotated using the Rapid Annotations using Subsystems Technology (RAST) server and the National Center for Biotechnology Information (NCBI) pipelines to establish the strain's probiotic potential. Phylogenetic analysis of L. plantarum LRCC5310 and related strains showed that LRCC5310 belonged to L. plantarum. However, comparative analysis revealed genetic differences between L. plantarum strains. Carbon metabolic pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database showed that L. plantarum LRCC5310 is a homofermentative bacterium. Furthermore, gene annotation results indicated that the L. plantarum LRCC5310 genome encodes an almost complete vitamin B6 biosynthetic pathway. Among five L. plantarum strains, including L. plantarum ATCC 14917T, L. plantarum LRCC5310 detected the highest concentration of pyridoxal 5'-phosphate with 88.08 ± 0.67 nM in MRS broth. These results indicated that L. plantarum LRCC5310 could be used as a functional probiotic for vitamin B6 supplementation.

Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the Drosophila warts (wts) Locus

The active form of vitamin B6, pyridoxal 5'-phosphate (PLP), is a cofactor for more than 200 enzymes involved in many metabolic pathways. Moreover, PLP has antioxidant properties and quenches the reactive oxygen species (ROS). Accordingly, PLP deficiency causes chromosome aberrations in Drosophila, yeast, and human cells. In this work, we investigated whether PLP depletion can also cause loss of heterozygosity (LOH) of the tumor suppressor warts (wts) in Drosophila. LOH is usually initiated by DNA breakage in heterozygous cells for a tumor suppressor mutation and can contribute to oncogenesis inducing the loss of the wild-type allele. LOH at the wts locus results in epithelial wts homozygous tumors easily detectable on adult fly cuticle. Here, we found that PLP depletion, induced by two PLP inhibitors, promotes LOH of wts locus producing significant frequencies of wts tumors (~7% vs. 2.3%). In addition, we identified the mitotic recombination as a possible mechanism through which PLP deficiency induces LOH. Moreover, LOH of wts locus, induced by PLP inhibitors, was rescued by PLP supplementation. These data further confirm the role of PLP in genome integrity maintenance and indicate that vitamin B6 deficiency may impact on cancer also by promoting LOH.

Drosophila carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes.

Pyridox(am)ine 5 ' -phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5 ' -phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in PNPO have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy. These patients often exhibit different types of seizures and variable comorbidities. Recently, the PNPO gene has also been implicated in epilepsy in adults. It is unclear how these phenotypic variations are linked to specific PNPO alleles and to what degree diet can modify their expression. Using CRISPR-Cas9, we generated four knock-in Drosophila alleles, hWT , hR116Q , hD33V , and hR95H , in which the endogenous Drosophila PNPO was replaced by wild-type human PNPO complementary DNA (cDNA) and three epilepsy-associated variants. We found that these knock-in flies exhibited a wide range of phenotypes, including developmental impairments, abnormal locomotor activities, spontaneous seizures, and shortened life span. These phenotypes are allele dependent, varying with the known biochemical severity of these mutations and our characterized molecular defects. We also showed that diet treatments further diversified the phenotypes among alleles, and PLP supplementation at larval and adult stages prevented developmental impairments and seizures in adult flies, respectively. Furthermore, we found that hR95H had a significant dominant-negative effect, rendering heterozygous flies susceptible to seizures and premature death. Together, these results provide biological bases for the various phenotypes resulting from multifunction of PNPO, specific molecular and/or genetic properties of each PNPO variant, and differential allele-diet interactions.

Antihyperlipidemic and Hepatoprotective Properties of Vitamin B6 Supplementation in Rats with High-Fat Diet-Induced Hyperlipidemia.

BACKGROUND: The incidence and mortality of hyperlipidemia are increasing year by year, showing a younger trend. At present, the treatment of hyperlipidemia is mainly dependent on western medicine, but its side effects on liver and kidney function are common in clinics. Therefore, it is necessary to study the treatment of hyperlipidemia by augmenting effective dietary nutrition supplements. Vitamin B6 (VitB6), as an essential cofactor for enzymes, participates in lipid metabolism. The effects of VitB6 on hyperlipidemia, however, have not been reported until now. AIM: The present study was to investigate the influence of VitB6 on hepatic lipid metabolism in hyperlipidaemia rats induced by a High-Fat Diet (HFD). METHODS: Male Sprague-Dawley rats were kept on HFD for two weeks to establish the hyperlipidemia model. The rats in low-dosage and high-dosage groups were received 2.00 and 3.00 mg/kg/- day of VitB6 for eight weeks, respectively. RESULTS: The results showed that both doses of VitB6 reduced HFD-induced hepatic Low-Density Lipoprotein Cholesterol (LDL-C); decreased blood cholesterol (TC), triglycerides, LDL-C, atherogenic index (AI), Atherogenic Index of Plasma (AIP), apolipoprotein B (ApoB) and ApoB/apolipoprotein A-1(ApoA1) ratio; increased liver High-Density Lipoprotein Cholesterol (HDL-C) and serum ApoA1; reduced hepatic steatosis and triglyceride accumulation, lowered fat storage, and recovered heart/body and brain/body ratio to a normal level. In addition, VitB6 supplementation markedly decreased HMGR level, increased the mRNA abundance of LDLR and CYP7A1, and protein expression of SIRT1, following the downregulation of SREBP-1 and PPARγ protein expression in the liver of hyperlipidemia rats. CONCLUSION: In summary, oral VitB6 supplementation can ameliorate HFD-induced hepatic lipid accumulation and dyslipidemia in SD rats by inhibiting fatty acid and cholesterol synthesis, promoting fatty acid decomposition and cholesterol transport.

Investigating the causality of metabolites involved in one-carbon metabolism with the risk and age at onset of Parkinson's disease: A two-sample mendelian randomization study.

With the aging population and increasing life expectancy, Parkinson's disease (PD), a neurological disorder rapidly increasing in morbidity and mortality, is causing a huge burden on society and the economy. Several studies have suggested that one-carbon metabolites, including homocysteine, vitamin B6, vitamin B12 and folate acid, are associated with PD risk. However, the results remain inconsistent and controversial. Thus, we performed a two-sample Mendelian randomization (MR) study to detect the causality between one-carbon metabolites and PD susceptibility as well as age at PD onset. We collected several genetic variants as instrumental variables from large genome-wide association studies of one-carbon metabolites (homocysteine: N = 14, vitamin B6: N = 1, vitamin B12: N = 10, folate acid: N = 2). We then conducted MR analyses using the inverse variance-weighted (IVW) approach and additional MR-Egger regression, weighted median and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods to further test causality. The results showed no causal association between circulating homocysteine levels and PD risk (p = 0.868) or age at PD onset (p = 0.222) with the IVW method. Meanwhile, similar results were obtained by three complementary analyses. In addition, we did not observe any evidence that the circulating levels of vitamin B6, vitamin B12 and folate acid affected the risk of PD or age at onset of PD. Our findings implied that lowering homocysteine levels through vitamin B6, vitamin B12 or folate acid supplementation may not be clinically helpful in preventing PD or delaying the age at PD onset.

Link between methyl nutrients and the DNA methylation process in the course of selected diseases in adults.

DNA methylation is a reversible epigenetic modification that plays a crucial role in transcriptional gene silencing. Both excessive (hypermethylation) and reduced DNA methylation (hypomethylation) can contribute to the disturbance of the proper course of many important processes in the human body. The aim of the study was to discuss the relationship between methyl nutrients and the DNA methylation process in the course of selected diseases in adults. Methyl nutrients include folates (vitamin B9), riboflavin (vitamin B2), cobalamin (vitamin B12), pyridoxine (vitamin B6) and choline (vitamin B4), as well as methionine and betaine. These substances play the role of both substrates and cofactors in transformations related to one-carbon metabolism. The deficiency of methyl nutrients in the body can lead to disturbances in SAM synthesis, which is the primary donor of methyl groups in the DNA methylation process. However, the mechanism explaining the discussed relationship has not been fully explained so far. Both the concentration in the body and the intake of folate and vitamin B12 in the diet can, to some extent, have an effect on the level of DNA methylation in healthy people. In comparison, data on the effect of excessive intake of vitamin B12 in the diet on the risk of cancer development are inconsistent. An adequate betaine and choline intake in the diet might not only affect the overall improvement of the DNA methylation profile, but, to some extent, also reduce the risk of cancer, the effect of which can depend on the content of folic acid in the body. Research results on the effect of supplementation of methyl nutrients on the DNA methylation process are inconclusive. It is therefore necessary to conduct further research in this area to draw clear conclusions.

Pyroluria: Fact or Fiction?

Objective: The term "Mauve factor" (pyrroluria) dates back to 1958 when Dr. Abram Hoffer defined the condition as elevated levels of pyrroles in the urine, currently called hydroxyhemepyrrolin-2-one (HPL). It was suggested that the raised pyrrole levels lead to depletions in zinc and vitamin B6, which, in turn, were hypothesized to result in a range of psychiatric disorders, such as schizophrenia, anxiety, and depression. Treatment implications are supplementation with zinc and B6. This article aimed to review the scientific literature associating pyrroluria with psychiatric symptoms, explore the validity of HPL testing, explore the role of nutrients as treatment options for pyrroluria, and discuss future research directions. Methods: A PRISMA review was conducted using search results from electronic databases PubMed, MEDLINE, PsycINFO, EMBASE from inception to February 2020 using the following keywords: hydroxyhemepyryrrolin (HPL), kryptopyrrole (KP), mauve factor, pyroluria, pyrroluria, monopyrroles. Article reference lists were also scanned and included where relevant. Results: Seventy-three articles were identified of which only three studies identified significantly higher HPL levels in a psychiatric population compared with controls, and there were no placebo-controlled treatment trials directed at pyrroluria. The other 13 clinical studies either showed no association or did not provide adequate data to show group differences in HPL levels. Despite an extensive history of practitioners diagnosing and treating a wide variety of mental health conditions associated with pyrroluria as well as clinical observations of elevated HPL being associated with psychiatric disorders, there was no clear research that showed the following: (1) elevated HPL is robustly associated with increased mental health symptoms, (2) elevated HPL in urine is associated with increased urine excretion of zinc and B6, and (3) high-dose zinc and B6 are an efficacious treatment for mental health problems associated with elevated HPL. Conclusions: Elevated HPL is a clinically observed, but poorly researched biomarker with unclear associations with mental disorders. Based on current evidence, HPL testing is not recommended as a screening or treatment tool. Further research is required in the following areas: establishment of which specific clinical populations exhibit elevated HPL, validation of the chemistry and validity of testing, and controlled trials to establish efficacy of high-dose zinc and B6 as treatment of elevated pyrroles.

Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism.

PDXK encodes for a pyridoxal kinase, which converts inactive B6 vitamers to the active cofactor pyridoxal 5'-phosphate (PLP). Recently, biallelic pathogenic variants in PDXK were shown to cause axonal Charcot-Marie-Tooth disease with optic atrophy that responds to PLP supplementation. We present two affected siblings carrying a novel biallelic missense PDXK variant with a similar phenotype with earlier onset. After detection of a novel PDXK variant using Whole Exome Sequencing, we confirmed pathogenicity through in silico protein structure analysis, determination of pyridoxal kinase activity using liquid chromatography-tandem mass spectrometry, and measurement of plasma PLP concentrations using high performance liquid chromatography. Our in silico analysis shows a potential effect on PDXK dimer stability, as well as a putative effect on posttranslational ubiquitination that is predicted to lead to increased protein degradation. We demonstrate that the variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels. Our patients' early diagnosis and prompt PLP replacement restored the PLP plasma levels, enabling long-term monitoring of clinical outcomes. We recommend that patients presenting with similar phenotype should be screened for PDXK mutations, as this is a rare opportunity for treatment.

Transcriptome analysis reveals the protection mechanism of proanthocyanidins for Saccharomyces cerevisiae during wine fermentation.

Grape-derived proanthocyanidins could act as a protector against various environmental stresses for Saccharomyces cerevisiae during wine fermentation, resulting in the increased physiological activity, fermentation efficiency and improved wine quality. In order to explore the possible protection mechanism of proanthocyanidins globally, RNA-seq analysis for wine yeast AWRI R2 cultivated with 0 g/L (group A), 0.1 g/L (group B), 1.0 g/L (group C) proanthocyanidins were applied in this study. Differentially expressed genes were enriched into six metabolic pathways including vitamin B6, thiamine, amino acids, aminoacyl-tRNA, carbohydrate and steroid based on KEGG enrichment analysis. Four key genes (SNZ2, THI6, THI21 and THI80), participated in the biosynthesis of vitamin B6 and thiamine, were up-regulated significantly in proanthocyanidins treated yeast cells and the gene expression levels were verified by RT-qPCR. Yeast cells supplemented with proanthocyanidins performed increased intracellular levels of vitamin B6 and thiamine and higher cell viability compared to the control group. In addition, the composition of intracellular fatty acids showed an obvious alternation in proanthocyanidins-treated yeast cells, in which the UFAs content increased whereas the SFA content decreased. In general, we provided an indirect protection effect of proanthocyanidins on the yeast cells to alleviate environmental stresses during wine fermentation.

Physical Activity, Nutritional Status, and Autonomic Nervous System Activity in Healthy Young Adults with Higher Levels of Depressive Symptoms and Matched Controls without Depressive Symptoms: A Cross-Sectional Study.

The aim of the present study was to comprehensively investigate physical activity (PA), nutritional status, and autonomic nervous system (ANS) activity in healthy young adults with higher levels of depressive symptoms and in sex- and age-matched controls without depressive symptoms. We recruited 35 healthy young adults with higher levels of depressive symptoms (DEP group) and 35 controls (CON group). Measurement items were daily number of steps, the duration and amount of PA ≥3 metabolic equivalents (METs), exercise habits, the consumption of tryptophan (TRP) and/or vitamin B6-rich foods, plasma levels of total TRP and vitamin B6 levels, and ANS activity. The DEP group had fewer daily steps, as well as duration and amount of PA ≥3 METs, than the CON group, while there was no difference in exercise habits. The intake frequency of TRP and/or vitamin B6-rich foods and plasma vitamin B6 levels of the DEP group were rather higher than those in the control group. Plasma TRP levels and ANS activity were comparable in the two groups. Our findings suggest that a decline in overall PA, including daily steps as well as duration and amount of moderate-to-vigorous-intensity PA, could be associated with higher levels of depressive symptoms in healthy young adults. Their dietary intake of TRP and/or vitamin B6-rich foods was adequate, and there was no ANS activity dysfunction.

Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.

Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.

The Vitamins Involved in One-Carbon Metabolisms are Associated with Reduced Risk of Breast Cancer in Overall and Subtypes.

Background: Some micronutrients like folate, vitamin B12, B6, and B2 are the source of coenzymes, which participate in one-carbon metabolism. Any disruption in this metabolism can interfere with DNA replication, repair and regulation of gene expression and ultimately promote the likelihood of carcinogenesis. This study aimed at investigating the relationship between the intakes of micronutrients involved in one-carbon metabolism with breast cancer (BrCa) and its subtype's odds. Methods: Nutrients' intake from diet and supplements were collected through interviewing 151 cases and 154 controls by a 168-item semiquantitative food frequency questionnaire. Logistic regression was used to determine the relationship between dietary and/or total intake of studied nutrients and odds of BrCa and its subtypes. Results: After adjusting the effects of confounding variables in the models, the odds of BrCa was significantly lower in the highest intake quartile compared with the lowest quartile for total intake of vitamin B2 (OR = 0.17, 95% CI, 0.07-0.39; Ptrend < 0.001), vitamin B6 (OR = 0.11, 95% CI, 0.05-0.27; Ptrend < 0.001), vitamin B12 (OR = 0.20, 95% CI, 0.09-0.43; Ptrend < 0.001) and folate (OR = 0.09, 95% CI, 0.04-0.21; Ptrend < 0.001). Also, those with the highest quartile of vitamin B6, B12, B2 and folate intake compared with the lowest quartile were less likely to develop estrogen receptor (ER)+ and progesterone receptor (PR)+ subtypes, ER- status, PR- and human epidermal growth factor receptor 2 (HER2)+ subtypes and HER2- status. Conclusion: High intakes of vitamins B2, B6 and folate are associated with reduced odds of BrCa in overall and all ER, PR and HER2 subtypes. Also, high intakes of vitamin B12 reduced the odds of all subtypes of BrCa except ER- subtype.

Multiple roles for Vitamin B6 in plant acclimation to UV-B.

Direct and indirect roles of vitamin B6 in leaf acclimation to supplementary UV-B radiation are shown in vitamin B6 deficient Arabidopsis thaliana mutant rsr4-1 and C24 wild type. Responses to 4 days of 3.9 kJ m-2 d-1 biologically effective UV-B dose were compared in terms of leaf photochemistry, vitamer content, and antioxidant enzyme activities; complemented with a comprehensive study of vitamer ROS scavenging capacities. Under UV-B, rsr4-1 leaves lost more (34%) photochemical yield than C24 plants (24%). In the absence of UV-B, rsr4-1 leaves contained markedly less pyridoxal-5'-phosphate (PLP) than C24 ones, but levels increased up to the C24 contents in response to UV-B. Activities of class-III ascorbate and glutathione peroxidases increased in C24 leaves upon the UV-B treatment but not in the rsr4-1 mutant. SOD activities remained the same in C24 but decreased by more than 50% in rsr4-1 under UV-B. Although PLP was shown to be an excellent antioxidant in vitro, our results suggest that the UV-B protective role of B6 vitamers is realized indirectly, via supporting peroxidase defence rather than by direct ROS scavenging. We hypothesize that the two defence pathways are linked through the PLP-dependent biosynthesis of cystein and heme, affecting peroxidases.

Fructus Gardeniae-induced gastrointestinal injury was associated with the inflammatory response mediated by the disturbance of vitamin B6, phenylalanine, arachidonic acid, taurine and hypotaurine metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardenia (FG) is a widely used bitter and cold herb for clearing heat and detoxicating. Currently, toxicity of FG and its relative formula has been reported in many clinical and animal studies. However, no systematic research has been carried out on FG-related gastrointestinal (GI) injury which has been emphasized in China since the Ming Dynasty. AIM OF THE STUDY: The purpose of this article is to investigate whether FG could damage GI and explore the mechanisms involved. MATERIAL AND METHODS: FG was given to male mice by 7-day intragastric administration at average doses of 0.90 g (L group), 1.50 g (M group), and 3.00 g (H group) crude drug/kg FG. Comprehensive understanding of changes in weight, diarrhea degree, stool routine, histomorphology and inflammatory factors of stomach, small intestine, and colon for evaluating the effect of different doses of FG on GI injury. Moreover, metabolomics-based mechanisms exploration of FG on GI injury was carried out via HPLC-Q-TOF/MS analysis on mice urine. RESULTS: High dose FG caused GI injury with serious diarrhea, decreased weight, abnormal stool routine, sever alteration in histomorphology of small intestine and colon (mild change in stomach), and significant change in inflammatory factors. The results of metabolomics suggested that 55 endogenous metabolites dispersed in 21 significantly altered metabolic pathways in 3.00 g/kg crude FG treated mice. The hub metabolites of GI injury were mainly related with vitamin B6 metabolism, phenylalanine metabolism, arachidonic acid metabolism, and taurine and hypotaurine metabolism via correlated network analysis. CONCLUSION: FG affected the normal functions of GI via the regulating a variety of metabolic pathways to an abnormal state, and our results provided a research paradigm for the GI-injury of the relative bitter and cold traditional Chinese medicines.

Novel metabolic disturbances in marginal vitamin B6-deficient rat heart.

Vitamin B6 deficiency is associated with cardiovascular disease (CVD). Although plasma biomarkers have been proposed, no studies have yet directly profiled heart tissue, and the mechanisms have to be fully defined. Thus, in order to provide better insight into vitamin B6-deficient effects on cardiac functions, we sought to identify the metabolic profile in heart tissue consequent to change in dietary vitamin B6 levels by applying metabolomics. Heart tissues of rats fed a basal diet containing a marginal vitamin B6-deficient, vitamin B6-recommended or vitamin B6-supplemented level were analyzed by metabolomics analysis. Among over 500 detected metabolites, imidazole metabolites including carnosine, anserine, homocarnosine and histamine exhibited the highest decrease upon vitamin B6 deficiency (>-45%, P<.01), along with their precursors ß-alanine, γ-aminobutyric acid (GABA) and 1-methylhistidine. Ornithine was the only metabolite exhibiting an increased level in the vitamin B6-deficient group. Vitamin B6 deficiency significantly attenuated the activity of heart tissue glutamate decarboxylase (GAD), although there was undetectable activity of aspartate decarboxylase (ADC), suggesting that the involvement of vitamin B6 in imidazole metabolite synthesis occurs partly through GABA production by regulating GAD rather than through a straightforward ß-alanine production pathway via ADC in the heart. Notably, vitamin B6 deficiency significantly attenuated citric acid cycle metabolite levels, suggesting cardiac energy metabolism impairment. This study provides a new link between vitamin B6 and cardiac functions, in which marginal vitamin B6 deficiency impairs imidazole and energy metabolism in heart. This newly revealed cardiac metabolic profile may reveal novel molecular targets or foodstuffs for CVD prevention.

Overexpression of PDX-II gene in potato (Solanum tuberosum L.) leads to the enhanced accumulation of vitamin B6 in tuber tissues and tolerance to abiotic stresses.

Vitamin B6 is a vital metabolite required for living organisms as a cofactor in several metabolic biochemical reactions and recognized as a potent antioxidant molecule which modulates the expression of the proteins responsible for the scavenging of cellular reactive oxygen species. It is well established that the microorganisms and plants can synthesize the B6 de novo, therefore, all the animals including humans must acquire it from the plant dietary resources. However, the bioavailability of the vitamin in the edible portions of the commonly consumed plants is insufficient to meet the daily recommended doses. Genetic engineering techniques have proven successful in increasing the vitamin B6 content in the model plants. Present study describe the development of transgenic potato (Solanum tuberosum L. cv. Kufri chipsona) overexpressing key vitamin B6 pathway gene, the PDXII (NCBI database Ref. ID- NM_125447.2) isolated from Arabidopsis thaliana under the control of CaMV 35S constitutive promoter. The stable integration and expression of transgene in the transgenic lines were confirmed by PCR, Southern blot and RT-PCR analysis. Transgenic tubers exhibited considerably improved vitamin B6 accumulation (up to 107-150%) in comparison to the untransformed controls potato. This increase in vitamin B6 was also correlated with the increased mRNA expression of PDXII gene. The prominent increase in the B6 content of transgenic potato was also associated with the capability to survive under abiotic stresses, therefore, the transgenic lines were able to withstand various abiotic stresses imposed by salinity (NaCl) or methyl viologen (MV). We thus demonstrated that overexpression of PDXII gene under the control of a constitutive promoter enhanced the accumulation of the vitamin B6 which also augmented the tolerance under various abiotic stresses in potato (Solanum tuberosum L.).

Parental micronutrient deficiency distorts liver DNA methylation and expression of lipid genes associated with a fatty-liver-like phenotype in offspring.

Micronutrient status of parents can affect long term health of their progeny. Around 2 billion humans are affected by chronic micronutrient deficiency. In this study we use zebrafish as a model system to examine morphological, molecular and epigenetic changes in mature offspring of parents that experienced a one-carbon (1-C) micronutrient deficiency. Zebrafish were fed a diet sufficient, or marginally deficient in 1-C nutrients (folate, vitamin B12, vitamin B6, methionine, choline), and then mated. Offspring livers underwent histological examination, RNA sequencing and genome-wide DNA methylation analysis. Parental 1-C micronutrient deficiency resulted in increased lipid inclusion and we identified 686 differentially expressed genes in offspring liver, the majority of which were downregulated. Downregulated genes were enriched for functional categories related to sterol, steroid and lipid biosynthesis, as well as mitochondrial protein synthesis. Differential DNA methylation was found at 2869 CpG sites, enriched in promoter regions and permutation analyses confirmed the association with parental feed. Our data indicate that parental 1-C nutrient status can persist as locus specific DNA methylation marks in descendants and suggest an effect on lipid utilization and mitochondrial protein translation in F1 livers. This points toward parental micronutrients status as an important factor for offspring health and welfare.

The Weight Loss Effects of Branched Chain Amino Acids and Vitamin B6: A Randomized Controlled Trial on Obese and Overweight Women.

Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25-34.9 kg/m2). Taking a four-week moderate deficit calorie diet (-500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (-2.43 ± 1.02 kg) or placebo (-1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.

Pyridoxine-Dependent Epilepsy in Zebrafish Caused by Aldh7a1 Deficiency.

Pyridoxine-dependent epilepsy (PDE) is a rare disease characterized by mutations in the lysine degradation gene ALDH7A1 leading to recurrent neonatal seizures, which are uniquely alleviated by high doses of pyridoxine or pyridoxal 5'-phosphate (vitamin B6 vitamers). Despite treatment, neurodevelopmental disabilities are still observed in most PDE patients underlining the need for adjunct therapies. Over 60 years after the initial description of PDE, we report the first animal model for this disease: an aldh7a1-null zebrafish (Danio rerio) displaying deficient lysine metabolism and spontaneous and recurrent seizures in the larval stage (10 days postfertilization). Epileptiform electrographic activity was observed uniquely in mutants as a series of population bursts in tectal recordings. Remarkably, as is the case in human PDE, the seizures show an almost immediate sensitivity to pyridoxine and pyridoxal 5'-phosphate, with a resulting extension of the life span. Lysine supplementation aggravates the phenotype, inducing earlier seizure onset and death. By using mass spectrometry techniques, we further explored the metabolic effect of aldh7a1 knockout. Impaired lysine degradation with accumulation of PDE biomarkers, B6 deficiency, and low γ-aminobutyric acid levels were observed in the aldh7a1-/- larvae, which may play a significant role in the seizure phenotype and PDE pathogenesis. This novel model provides valuable insights into PDE pathophysiology; further research may offer new opportunities for drug discovery to control seizure activity and improve neurodevelopmental outcomes for PDE.