Nutritional Genomics Uncovers Vitamin B3 Therapy as Curative for NAXD Disease
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE304377 | GEO | 2026/02/06
REPOSITORIES: GEO
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Project description:Nutritional Genomics Uncovers Vitamin B3 Therapy as Curative for NAXD Disease
| PRJNA1301136 | ENA
Project description:Vitamins are critical regulators of cellular processes, yet their influence on mRNA modifications, particularly N6-methyladenosine (m6A), remains poorly understood. This study investigates the effects of various vitamins (VB2, VB6, and VB12) on the mRNA m6A epitranscriptome in multiple mouse tissues (brain, liver, and testis). Clustering analyses revealed closer similarity between brain and testis m6A profiles, while the liver exhibited a unique signature, reflecting tissue-specific regulatory dynamics. Notably, over 90% of vitamin-specific m6A sites did not correlate with mRNA abundance, highlighting the role of m6A as a post-transcriptional regulator. Pathway enrichment analyses further revealed tissue- and vitamin-specific adaptations. Key genes responsive to vitamin treatments emerged as central regulators of m6A dynamics, aligning with the known roles of vitamins in metabolism, neural plasticity, and gene expression.
2026-04-03 | GSE286253 | GEO
Project description:The pharmacological significance of B vitamins, essential for various metabolic processes, and the therapeutic potential of probiotics in gastrointestinal health have been well-documented. However, the interactions between these entities remain poorly understood. In this study, we endeavored to elucidate the potential interplay between B vitamins and probiotics utilizing liquid chromatography-triple quadrupole mass spectrometry, pharmacokinetic modeling, and 16S rRNA gene sequencing. Employing healthy and pseudo-germ-free rat models, we revealed that probiotics significantly improve the absorption of B1, B3, B5, and B12, and that the gut microbiota played a mediating role in this enhanced absorption of B vitamins by probiotics. High-throughput genetic sequencing uncovered a synergistic effect of B vitamins and probiotics in modulating the gut microbiota, particularly increasing the abundance of Verrucomicrobia and Akkermansia. Furthermore, in vitro experiments demonstrated that probiotics used in this study had a relatively minor influence on the production and permeability of B vitamins, while B vitamins did not significantly contribute to the growth, auto-aggregation, and adhesion of probiotics. In summary, a complex network connection exists between B vitamins and probiotics, wherein the gut microbiota emerges as a pivotal factor that cannot be overlooked.
2024-07-31 | GSE253146 | GEO
Project description:Distinct markers for early, mild vitamin B3 deficiency are lacking. To identify these, we examined the molecular responses of white adipose tissue to vitamin B3 withdrawal. We performed a dietary intervention in male C57Bl/6JRcc mice. A diet with a low but adequate level of tryptophan without nicotinamide riboside (NR) was compared to the same diet with NR at the recommended vitamin B3 (30 mg NR per kg diet). Physiological and circulating parameters were determined and global transcriptomics, qRT-PCR and histology of epididymal white adipose tissue (eWAT) were done. We observed a decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation. This was consistent with molecular changes in eWAT, where we observed an altered MEK/ERK signalling, a lowering of glucose utilization markers and an increase in makers of fatty acid catabolism, which may be related to the consistent reduction of mitochondrial OXPHOS Complex I (mRNAs and protein). The synthesis pathway of tetrahydropteridine (BH4), an essential cofactor for neurotransmitter synthesis, was found to be increased. Based on our results, we propose the technically validated downregulation of Anp32a, Tnk2 and the upregulation of Mapk1, Map2k1, Mthfs, Mthfsl and Qdpr as a WAT transcriptional signature marker for mild vitamin B3 deficiency.
2019-05-06 | GSE116483 | GEO
Project description:Saccharomyces cerevisiae is bradytroph for class B vitamins, it means that yeast cells exhibit slower growth in the absence of an external source of these metabolites. Alleviating these nutritional requirements for optimal growth performance would represent a valuable phenotypic characteristic for industrial strains since this would result in cheaper processes that would also be less susceptible to contaminations. In the present study, suboptimal growth of S. cerevisiae in absence of either pantothenic acid, para-aminobenzoic acid (pABA), pyridoxine, inositol and biotin were corrected by single or double gene overexpression of ScFMS1, ScABZ1/ScABZ2, ScSNZ1/ScSNO1, ScINO1 and the Cyberlindnera fabianii BIO1, respectively. Several strategies were attempted to improve growth of S. cerevisiae CEN.PK113-7D in absence of thiamine, revealing that overexpression of ScTHI4 and ScTHI4/ScTHI5 improved growth up to 83% of the maximum specific growth rate of the reference CEN.PK113-7D in vitamins containing medium. By combining overexpression of solely seven S. cerevisiae genes and the heterologous CfBIO1, the strain IMX2816 was fast-growing at a maximum specific growth rate of 0.33 ± 0.01 h-1 in medium devoid of all vitamins. Secondly, this strain exhibited physiological performances in oxic glucose-limited chemostat cultures at a dilution rate of 0.1 h-1 in absence of vitamins similar to that of the reference strain CEN.PK113-7D grown in fully supplemented medium. These physiological similarities were further emphasized by the limited differences observed in comparative transcriptome analysis from the chemostat culture grown cells that were essentially affecting genes of the class B vitamins biosynthetic pathways. This work paves the way towards construction of the first fast growing vitamin-independent S. cerevisiae strain.
2023-02-21 | GSE225473 | GEO
Project description:Saccharomyces cerevisiae is bradytroph for class B vitamins, it means that yeast cells exhibit slower growth in the absence of an external source of these metabolites. Alleviating these nutritional requirements for optimal growth performance would represent a valuable phenotypic characteristic for industrial strains since this would result in cheaper processes that would also be less susceptible to contaminations. In the present study, suboptimal growth of S. cerevisiae in absence of either pantothenic acid, para-aminobenzoic acid (pABA), pyridoxine, inositol and biotin were corrected by single or double gene overexpression of native FMS1, ABZ1/ABZ2, SNZ1/SNO1, INO1 and the Cyberlindnera fabianii BIO1, respectively. Several strategies were attempted to improve growth of S. cerevisiae CEN.PK113-7D in absence of thiamine, revealing that overexpression of THI4 and THI4/THI5 was able to improve growth up to 83% of the maximum specific growth rate of the reference CEN.PK113-7D in medium including all vitamins. Although the initial aim of this study was to combine all identified mutations in a single strain, the engineered strain IMX2210 only harboured genes to correct biotin, pABA, pantothenate and inositol bradotrophies. Firstly, this strain was fast-growing at a maximum specific growth rate of 0.28 ± 0.01 h-1 in medium devoid of all vitamins. Secondly, this strain exhibited physiological variables in aerobic glucose limited chemostat cultures at a dilution rate of 0.1 h-1 in absence of vitamins similar to that of the reference strain CEN.PK113-7D grown in the same conditions but in a fully supplemented complete medium. These physiological similarities were further emphasized by the limited differences observed in comparative transcriptome analysis from the chemostat culture grown cells that were essentially affecting genes of the class B vitamins biosynthetic pathways. This work paves the way towards construction of the first fast growing vitamin-independent S. cerevisiae strain.
2023-12-01 | GSE191212 | GEO
Project description:Vitamin D deficiency and mutations in Vitamin D Receptor (VDR) are associated with liver disease and obesity, but the functions of vitamin D signaling in metabolism are poorly understood. Though vitamin D signaling is best known for its functions in mineral homeostasis and skeleton calcification in terrestrial vertebrates, this is unlikely to be the evolutionary function of vitamin D signaling. We utilize tissue-specific genetic modulation of Vdr signaling to investigate the function of the vitamin D endocrine system in zebrafish. We find that hepatocyte Vdr regulates organismal response to nutritional cues and coordinates hepatic and organismal energy metabolism by balancing energy storage and tissue growth.
2023-04-20 | GSE217120 | GEO
Project description:Histone post-translational modifications (PTMs) controls the gene expression profile via transcriptional regulation．Aberrant histone PTMs chromatin structures lead to dysregulated gene expression and cancer progression. Nicotinic acid (vitamin B3 or vitamin PP), one of the thirteen essential vitamins, has a wide range of uses, helping to function digestive system, skin and nervous system. Here we show nicotinic acid (NA) induces histone and non-histone lysine nicotinylation, and identify 17 nicotinylation sites on core histones in HeLa cells. Also, NA-derived nicotinylation of histone lysine residues is an epigenetic modification that regulates gene transcription via altering the chromatin accessibility by generating nicotinyl-CoA. Knic inactivates oncogene PPFIA1 transcription by inhibiting its combination with transcription factors HOXB9, and PPFIA1 was found as an important role in promoting cells spreading on the extracellular matrix and is required for migration and invasion in human breast tumor cells However, the role and the molecular mechanisms of PPFIA1 control hepatocellularcarcinoma (HCC) initiation and progression are poorly understood. Here we demonstrate PPFIA1 promotes proliferation, migration, invasion and tumorigenesis of HCC in vivo and in vitro. It is worth noting that the expression of PPFIA1 is upregulated in multiple human carcinomas, including HCC. Our study also suggests that PPFIA1 is a promising potential target of NA for the future treatment strategies of HCC
2026-04-13 | GSE229949 | GEO
Project description:Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure. Recent reports have characterized the nature of hPXR-mediated hepatotoxicity and systemic toxicity of antitubercular drugs. The antitubercular drug isoniazid plays a role in such pathologic states as acute intermittent porphyria, anemia, hepatotoxicity, hypercoagulable states (deep vein thrombosis, pulmonary embolism, or ischemic stroke), pellagra (vitamin B3 deficiency), peripheral neuropathy, and vitamin B6 deficiency. However, the mechanisms by which isoniazid administration leads to these states are unclear. To elucidate the mechanism of rifampicin- and isoniazid-induced liver and systemic injury, we performed tandem mass tag mass spectrometry-based proteomic screening of mPxr–/– and hPXR mice treated with combinations of rifampicin and isoniazid. Proteomic profiling analysis suggested that the hPXR liver proteome is affected by antitubercular therapy to disrupt [Fe–S] cluster assembly machinery, [2Fe–2S] cluster-containing proteins, CYP450 enzymes, heme biosynthesis, homocysteine catabolism, oxidative stress responses, vitamin B3 metabolism, and vitamin B6 metabolism. These findings provide insight into the etiology of some of these processes and potential targets for subsequent investigations.
2020-07-19 | PXD019505 | Pride
Project description:Folate, and its synthetic form folic acid, function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-PROOF study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of two years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n=44 folic acid/vitamin B12, n=43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo, revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8 and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425 and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.
2015-11-16 | GSE74548 | GEO