NAD+ flux is maintained in aged mice

McReynolds, Melanie R.; Chellappa, Karthikeyani; Chiles, Eric; Jankowski, Connor S.R.; Chen, Li; Descamps, Hélène C.; Mukherjee, Sarmistha; Bhat, Yashaswini R; Chu, Qingwei; Botolin, Paul; Thaiss, Cristoph; Lu, Wenyun; Su, Xiaoyang; Rabinowitz, Joshua D.; Baur, Joseph A.

doi:10.21203/rs.3.rs-86538/v1

Cited by 4 publications

(2 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, because NAD + flux does not strongly correlate with the protein expression of its biosynthetic or consuming enzymes (38), this hypothesis will need to be properly tested in future studies using in vivo NAD + flux measurements. That said, available flux measurements from aged mice, a wellestablished model of diastolic dysfunction, indicate that increased NAD + consumption-not impaired production-causes the agerelated NAD + decline (39). This may have major implications for the choice of the optimal NAD + precursor for either form of heart failure.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide for the treatment of heart failure with preserved ejection fraction

et al. 2021

View full text Add to dashboard Cite

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Nicotinamide for the treatment of heart failure with preserved ejection fraction

et al. 2021

View full text Add to dashboard Cite

show abstract

“…It is important to note that NAD + levels have also been shown to decline in the intestine with healthy aging (115)(116)(117). However, it is currently unknown if declining NAD + levels within the intestine renders a person more susceptible to intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation

Novak,

Crawford,

Mentrup

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

IntroductionWe have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor–gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.MethodsMice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study.ResultsWe demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis.DiscussionOur results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients.

show abstract

Mechanisms of probiotic Bacillus against enteric bacterial infections

et al. 2023

View full text Add to dashboard Cite

Gastrointestinal infection is a leading cause of gut diseases attracting global health concerns. The emerging antimicrobial resistance in enteric pathogens drives the search of viable and renewable alternatives to antibiotics for the health of both human beings and animals. Spore-forming probiotic Bacillus have received extensively interests for their multiple health benefits, including the restoration of microbiota dysbiosis and the reduction of drug-resistant pathogens. These promising benefits are mainly attributed to the activity of structurally diverse Bacillus-derived metabolites, such as antibacterial compounds, short-chain fatty acids, and other small molecules. Such metabolites show the capacity to directly target either the individual or community of bacterial pathogens, and to potentiate both host cells and gut microbiota. The better understanding of the mechanisms by which probiotic Bacillus and the metabolites modulate the metabolism of hosts and microbiota will advance the screening and development of probiotic Bacillus. In this review, we discuss the interaction among probiotic Bacillus, microbiota and host, and summarize the Bacillus-derived metabolites that act as key players in such interactions, shedding light on the mechanistic understanding of probiotic Bacillus against enteric bacterial infections.

show abstract

NAD+ flux is maintained in aged mice

Cited by 4 publications

References 58 publications

Nicotinamide for the treatment of heart failure with preserved ejection fraction

Nicotinamide for the treatment of heart failure with preserved ejection fraction

Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation

Mechanisms of probiotic Bacillus against enteric bacterial infections

Contact Info

Product

Resources

About