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This study demonstrated that...NAD+ metabolism governs the anti-inflammatory function of mesenchymal stem cells during inflammation.

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A rare mutation that disorganizes keratin filaments, and causes skin blistering and liver injury, can be treated with parthenolide, which has the effect of upregulating SIRT2. Giving mice NMN had a protective effect similar effect to parthenolide.

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In this study, we report for the first time that nicotinamide riboside (NR) supplementation could alleviate cancer metastasis in tumor-bearing mice and enhance the maintenance of body weight at the late stage of cancer. Our results reveal that NAD precursor may be a novel treatment for the prevention of HCC progression....,NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice...NR supplementation decreased metastasis to the bone and liver...NR supplementation also significantly decreased the size of allografted tumors and extended the survival time... In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of liver cancer progression.

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Our data suggested that normalizing NADH:NAD+ ratio with NR may be a potential treatment for glycolytic and fatty acid β-oxidation defects in citrin deficiency in the liver. Additionally, increasing cytoplasmic NAD+ levels may be useful for the treatment of other monogenic mitochondrial diseases involving the aspartate malate shuttle and mitochondrial transporters

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Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis....Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.

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This study shows that NAMPT inhibition concomitant to NAD restoration significantly attenuate experimental liver damage.

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NAFLD is the most common form of liver disease, but there are no licensed medications available for its treatment. The progression of NAFLD is closely related to chronic inflammation, insulin resistance, and lipid accumulation. NAD+ is currently considered as a potential therapeutic target for NAFLD. As the critical NAD+ degrading enzyme in mammals, inhibiting of CD38 can significantly increase NAD+ levels and prevent NAFLD progression. These ideas have been confirmed in animal studies, but clinical trials still need to be verified.

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The study underscores the importance of amino acid and NAD+supplementation as promising strategies in fatty liver disorder.

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We demonstrate supplementing with nicotinamide (NAM) and related components of this pathway improve mitochondrial and overall hepatic metabolic dysfunction. We find that the effects of modulating the TRP-NAD+ pathway are mediated through SIRT1...NAM treatment can either reduce mitochondria degradation or increase its biogenesis in our model of severe malnutrition...NAM was shown to increase SIRT1 levels. The effect was not specific to NAM, as Nicotinamide Riboside (NR) and Tryptophan (TRP) demonstrated a similar effect...In our study, NAM treatment did not significantly restore NAD+ levels whereas NR did...

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CD38 inhibition can be suggested as a strategy to boost NAD+ and would not negatively affect hepatic functions during thermogenesis.

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This specific combination of metabolic cofactors [including nicotinamide riboside] can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally on a path to becoming the most frequent cause of chronic liver disease. Novel strategies for the prevention and treatment of NAFLD are urgently needed. A 6-month prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy of daily NRPT (commercially known as Basis; a combination of nicotinamide riboside and pterostilbene) supplementation in 111 adults with NAFLD...This study demonstrates that NRPT at the recommended dose is safe and may hold promise in lowering markers of hepatic inflammation in patients with NAFLD.

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...We previously reported that NR supplementation prevented the development of liver fibrosis in male mice. However, whether NR exerts a similar effect in females is unknown. Therefore, we determined whether NR supplementation can prevent obesity-induced inflammation and fibrosis in the liver and white adipose tissue (WAT) by providing NAD+ in obese female mice...Our results indicated that NR supplementation exerted an anti-obesity effect and prevented the development of inflammation and fibrosis in the white adipose tissue of old, but not young, female mice with diet-induced obesity.

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Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) [l-carnitine tartrate to facilitate mitochondrial fatty acid uptake from cytosol, the NAD+ precursor nicotinamide riboside to induce hepatic mitochondrial β-oxidation and facilitate fatty acid transfer through the mitochondrial membrane, and the potent glutathione precursors L-serine and N-acetyl-l-cysteine to reduce oxidative stress] promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver...In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.

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Together, our data establish an essential role for the mitochondrial sirtuin SIRT3 in liver regeneration and provide mechanistic insight into the beneficial effects of NR. Loss of SIRT3 results in mitochondrial dysfunction, lipid accumulation, and loss of hepatocyte replication in the regenerating liver. Although increasing NAD concentration is sufficient to accelerate mitochondrial metabolism in hepatocytes or the regenerating liver, the effect is independent of both SIRT3 and its nuclear counterpart SIRT1...We identify SIRT3 as a critical new player in liver regeneration and show that NAD supplementation influences metabolism independently of both SIRT1 and SIRT3.

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...In HFD-induced NAFLD mice model, NR displayed remarkable therapeutic effects on body weight gain, hepatic steatosis, steatohepatitis, insulin resistance, mitochondrial dysfunction, apoptosis and fibrosis...The findings from this research for the first time demonstrate that NAD+-boosting therapy reverses NAFLD by regulating SIRT2-deppendent Fndc5 deacetylation and deubiquitination, which results in a stimulation of Fndc5/irisin, a novel exerkine. These results suggest that Fndc5/irisin may be a potential nexus between physical exercise and NAD+-boosting therapy in metabolic pathophysiology.

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...This study aimed to explore the effects of nicotinamide riboside (NR) on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice. NR significantly improved liver histopathological damage and abnormal liver function... Therefore, NR supplementation has the potential to prevent Alcoholic Liver Disease (ALD), and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora-bile acid axis.

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...Seventy-two human liver specimens were analyzed, including 43 with alcohol-related liver disease...Liver samples from people with ArLD show depressed NAD+ and precursor levels as well as depressed myeloperoxidase activity.

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These data constitute the first report of the NAD+ metabolome in human liver biopsies. Using samples from explanted and resected liver tissue, we show that the concentration of NAD+ and precursor molecules are significantly lower in ArLD compared to other liver diseases and NL tissue. The concentration of NAD+ is inversely correlated with disease activity...Liver samples from people with Alcohol-related Liver Disease show depressed NAD+ and precursor levels as well as depressed myeloperoxidase activity.

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We suggest that NR initially mobilizes fat from the liver and, as the liver clears steatosis, glycemic control improves through a mechanism that does not involve direct insulin sensitization