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Urolithin A and Nicotinamide Riboside differentially regulate innate immune defenses and metabolism.

ABSTRACT: Urolithin A and Nicotinamide Riboside differentially regulate innate immune defenses and metabolism.

PROVIDER: PRJNA1106041 | ENA |

REPOSITORIES: ENA

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Urolithin A and Nicotinamide Riboside differentially regulate innate immune defenses and metabolism.

Project description:During aging, general cellular processes such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses become compromised. Urolithin A (UA) and NAD+ supplementation stimulate mitophagy, reduce pathological plaque load, and inflammation while improving learning in models of Alzheimer’s disease (Hou et al 2021; Fang et al 2019). Here we have performed a During aging, general cellular processes such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses become compromised. Urolithin A (UA) and NAD+ supplementation stimulate mitophagy, reduce pathological plaque load, and inflammation while improving learning in models of Alzheimer’s disease (Hou et al 2021; Fang et al 2019). Here we have performed a pairwise analysis of UA and nicotinamide riboside (NR) to investigate how these compounds modulate inflammation. The role of microglia in driving neuroinflammation is becoming more recognized in several neurodegenerative diseases, yet the effects of these drugs on microglia cells have not been thoroughly investigated. As both UA and NR are recognized as safe dietary supplements, their function in normal cells is equally important to understand as in a disease state. Here we investigated the effects of UA and NR in the human microglia cell line, HMC3.

2024-12-19 | GSE266162 | GEO

Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis

Project description:Abstract: Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr −/−.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (−17%) and hepatic steatosis (−22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.

2019-09-04 | GSE136821 | GEO

RNA-sequencing analysis of murine Hematopoietic Stem Cells treated with Nicotinamide Riboside

Project description:RNA-sequencing analysis of murine Hematopoietic Stem Cells treated with Nicotinamide Riboside

| PRJNA515529 | ENA

Nicotinamide riboside supplementation confers modest effects on skeletal muscle metabolism without mitochondrial and acetyl-proteome remodelingNicotinamide riboside supplementation confers modest effects on skeletal muscle metabolism without mitochondrial and acetyl-proteome remodeling

Project description:Nicotinamide riboside supplements (NRS) have been touted as a nutraceutical that promotes cardiometabolic and musculoskeletal health by enhancing nicotinamide adenine dinucleotide (NAD+) biosynthesis, mitochondrial function and/or the activities of NAD-dependent sirtuin deacetylase enzymes. This investigation examined the impact of NRS on whole body energy homeostasis, skeletal muscle mitochondrial function, and corresponding shifts in the acetyl-lysine proteome, in the context of diet-induced obesity using C57BL/6NJ mice. The study also included a genetically-modified mouse model that imposes greater demand on sirtuin flux and associated NAD+ consumption, specifically within muscle tissues. In general, whole body glucose control was modestly improved by NRS when administered at the midpoint of a chronic high fat diet, but not when given as a preventative therapy upon initiation of the diet. Contrary to anticipated outcomes, the study produced little evidence that NRS increases tissue NAD+ levels, augments mitochondrial function and/or mitigates diet-induced hyperacetylation of the skeletal muscle proteome.

2022-02-17 | PXD027904 | Pride

Nicotinamide Riboside is Uniquely Bioavailable in People and Mice

Project description:Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we conducted experiments to determine the time and dose-dependent effects of NR on blood, liver and heart NAD+ metabolism in people and mice. We report that human blood cell NAD+ can rise as much as 2.7-fold with a single dose of NR, that NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid (NA) and nicotinamide (Nam), and that single doses of 100, 300, and 1000 mg of NR provide a dose-dependent increase in the blood cell NAD+ metabolome in the first clinical trial of NR pharmacokinetics. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for conversion of NR to NAD+, is formed from NR and that the rise in NAAD is a highly sensitive biomarker of effective NAD+ supplementation.

2016-09-09 | MTBLS368 | MetaboLights

Hepatocyte-specific knockout of Nicotinamide phosphoribosyltransferase increases susceptibility for liver fibrosis in mice

Project description:We investigated the plasma and liver proteome changes in liver fibrosis in mice induced by hepatocyte-specific knockout of nicotinamide phosphoribosyltransferase (Nampt) upon a low-methionine, choline-free 60% high-fat (MCD) diet at multiple time points. We also investigated whether supplementation with nicotinamide riboside could alleviate liver injury and how the liver proteome changes upon NR supplementation.

2021-11-04 | PXD017170 | Pride

Voluntary running and IV nicotinamide riboside synergise to boost mouse skeletal muscle NAD+ without impacting OXPHOS capacity or insulin sensitivity

Project description:In clinical trials, oral supplementation with nicotinamide riboside (NR) fails to increase muscle mitochondrial respiratory capacity and insulin sensitivity, but also does not increase muscle NAD+ levels. This study tests the feasibility of chronically elevating skeletal muscle NAD+ in mice and investigates the putative effects on mitochondrial respiratory capacity, insulin sensitivity, and gene expression. Accordingly, to improve bioavailability to skeletal muscle, we developed an experimental model for administering NR repeatedly through a jugular vein catheter. Mice on a Western diet were treated with various combinations of NR, pterostilbene (PT), and voluntary wheel running, but metabolic effects of NR and PT treatment were modest. We conclude that chronic elevation of skeletal muscle NAD+ by intravenous injection of NR is possible but does not affect muscle respiratory capacity or insulin sensitivity in either sedentary or physically active mice. Our data have implications for NAD+ precursor supplementation regimes.

2022-02-08 | GSE194193 | GEO

Nicotinamide riboside augments the human skeletal muscle NAD+ 1 metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial

Project description:NAD+is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

2019-08-29 | GSE133261 | GEO

Untargeted proteomics on Enterocloster bolteae DSM 15670 Treated with urolithin C

Project description:Urolithin A is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota which can affect host health. Most, but not all, individuals harbor a microbiota capable of urolithin A production; however, the enzymes that dehydroxylate its dietary precursor, urolithin C, are unknown. Here, we used a combination of transcriptomics and proteomics to reveal a urolithin C dehydroxylase (ucd) operon that dehydroxylates 9-hydroxy urolithin compounds in Enterocloster spp. Using comparative genomics, we identified Lachnoclostridium pacaense as a novel urolithin C metabolizer. Biochemical characterization and structure predictions of proteins in the Ucd complex demonstrated that dehydroxylation was both NADH- and molybdopterin-dependent and used urolithin C as a terminal electron acceptor. A meta-analysis publicly available metagenomic data revealed that both bacteria and ucd operon genes are widely distributed in gut metagenomes and likely comprise keystone species in the metabolism of urolithins by the human gut microbiota.

2024-12-16 | PXD048514 | Pride

NAD + Supplementation by Nicotinamide Riboside Alters Function of Murine Hematopoietic Stem Cells from Impaired Environments

Project description:NAD + Supplementation by Nicotinamide Riboside Alters Function of Murine Hematopoietic Stem Cells from Impaired Environments

| PRJNA615893 | ENA