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.
Project description:Transcriptional profiling of mouse white adipose tissues The objective of this study is to explore the relationship between vitamin B6 activity and chronic inflammation of white adipose tissue in mice fed a high-fat diet. Twenty-four CD-1 mice were divided into two groups (n = 12) and fed either a 1 mg pyridoxine (PN) HCl /kg diet or a 35 mg PN HCl /kg diet for 8 weeks. We isolated total RNA from epididymal white adipose tissue of each group and compared gene expression profiles by DNA microarray data analysis. Noriyuki Yanaka
Project description:Transcriptional profiling of mouse white adipose tissues The objective of this study is to explore the relationship between vitamin B6 activity and chronic inflammation of white adipose tissue in mice fed a high-fat diet. Twenty-four CD-1 mice were divided into two groups (n = 12) and fed either a 1 mg pyridoxine (PN) HCl /kg diet or a 35 mg PN HCl /kg diet for 8 weeks. We isolated total RNA from epididymal white adipose tissue of each group and compared gene expression profiles by DNA microarray data analysis.
Project description:ScopeDistinct markers for mild vitamin B3 deficiency are lacking. To identify these, the molecular responses of white adipose tissue (WAT) to vitamin B3 withdrawal are examined.Methods and resultsA dietary intervention is performed in male C57BL/6JRccHsd mice, in which a diet without nicotinamide riboside (NR) is compared to a diet with NR at the recommended vitamin B3 level. Both diets contain low but adequate level of tryptophan. Metabolic flexibility and systemic glucose tolerance are analyzed and global transcriptomics, qRT-PCR, and histology of epididymal WAT (eWAT) are performed. A decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation in response to vitamin B3 withdrawal are observed. This is consistent with molecular changes in eWAT, including an activated MEK/ERK signaling, a lowering of glucose utilization markers, and an increase in makers of fatty acid catabolism, possibly related to the consistent lower expression of mitochondrial electron transport complexes. The synthesis pathway of tetrahydropteridine (BH4), an essential cofactor for neurotransmitter synthesis, is transcriptionally activated. Genes marking these processes are technically validated.ConclusionThe downregulation of Anp32a, Tnk2 and the upregulation of Mapk1, Map2k1, Qdpr, Mthfs, and Mthfsl are proposed as a WAT transcriptional signature marker for mild vitamin B3 deficiency.
Project description:Vitamins are essential metabolites that must be obtained from external sources. All 13 vitamins were identified in the early 1900s, a rich era of biochemistry. More recently, they are consumed indiscriminately. We introduce a new nutritional genomics framework that begins with a treatment and identifies all potential disease candidates. Using a genome-wide CRISPR screen at varying vitamin B3 levels, we nominated dozens of diseases for B3-based therapy. The top candidate was NAXD, a proofreading enzyme involved in correcting an aberrant form of NADH (NADHX). Mutations in NAXD cause severe neurodevelopmental disease, with no proven therapies. We created a new mouse model of disease, observing NADHX accumulation and NAD+ depletion in affected organs, leading to impaired serine biosynthesis. Low B3 diets worsened the disease, while B3 supplementation was curative, extending lifespan by more than 20-fold. This work introduces a new approach to nutritional genomics and precision vitamin therapies.
Project description:The aim of this study was to identify genes expressed selectively in brown adipose tissue as compared to white adipose tissue from the same animals. This analysis provides a gene set that is brown and white adipose selective. Keywords: tissue comparison from mice
Project description:The aim of this study was to identify genes expressed selectively in brown adipose tissue as compared to white adipose tissue from the same animals. This analysis provides a gene set that is brown and white adipose selective. Experiment Overall Design: Interscapular brown adipose tissue and epididymal white adipose tissue was carefully dissected from 3 male C57Bl/6 mice. These samples were profiled independently using Affymetrix mouse 430_2 gene arrays, representing 3 biological replicates for each brown and white adipose tissues.
Project description:White adipose tissue is a central place to energy storage and a major endocrine organ. However, adipose molecular mechanisms have been poorly studied during prolonged fasting. To fill this gap, the aim of this study was to decipher proteomic regulations in rat adipose tissue during phase 2 (lipid mobilization) and phase 3 (protein catabolism) of prolonged fasting compared to the fed state. Specific responses reflecting adipose tissue inflammation, increased fibrinolysis and a possible protein catabolism-related energy saving mechanism were recorded during phase 3. Differences between internal and subcutaneous adipose tissues were essentially related to lipid metabolism, the response to oxidative stress and energy production. These data thus provide a molecular basis of adipose tissue responses according to the fasting stage.
Project description:Adult mouse were kept at room temperature, RNAseq was performed for interscapular brown, subscapular white and inguinal white adipose tissue