Nicotinamide mononucleotide treatment improves spermatogenesis in obese mice by reducing lysine acetylation of lactate dehydrogenase C
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Xiaocan Lei
PROVIDER: PXD068628 | iProX | Fri Sep 19 00:00:00 GMT+01:00 2025
REPOSITORIES: iProX
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Project description:Elevated ambient temperature results in heat stress which is a major concern for productivity and product quality due to its negative impact on animal health, productivity and product quality. As global warming becomes more and more serious, the impact of heat stress (HS) on animal husbandry cannot be ignored. However, the effect of NMN on the quality of porcine oocytes after heat stress and the prevention strategies are not yet fully understood. Here, we report that nicotinamide mononucleotide (NMN) treatment ameliorates the quality of porcine oocytes exposed to heat stress. Specifically, we found that HS caused oocyte meiosis failure by disrupting the dynamics and arrangement of meiotic organelles, showing obvious damage to cytoskeleton assembly. Furthermore, heat stress can cause damage to oocyte mitochondria, which is an indicator of oocyte cytoplasmic maturation. On the contrary, supplementation of NMN can improve this phenomenon, maintain the normal chromosome/spindle structure, and the dynamics of CGs and its core content ovastacin.
2022-06-22 | GSE185338 | GEO
Project description:NAD+ levels decline in multiple tissues over age, causing various age-associated pathophysiologies. Nicotinamide mononucleotide (NMN) is a key NAD+ intermediate that promotes NAD+biosynthesis and counteracts age-associated physiological decline. However, how NMN transport is regulated remains unknown. Here we report a novel NMN transporter encoded by the Slc12a8 gene. Slc12a8 is highly expressed and regulated by NAD+ in the small intestine. Knocking down this gene abrogates the transport of NMN in vitro and in vivo. Slc12a8 exhibits specificity to NMN and dependency on the sodium ion. Slc12a8 deficiency significantly decreases NAD+ levels in the jejunum and ileum, due to decreases in NMN uptake traced by doubly labeled isotopic NMN. Slc12a8 expression is upregulated in the aged ileum, contributing to the maintenance of NAD in aged mice. Thus, this newly identified NMN transporter plays a critical role in counteracting NAD+ decline during aging.
2019-01-01 | GSE118365 | GEO
Project description:Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a novel intervention against diet- and age-induced T2D. 4 regular chow fed mice (RC1-4) vs 4 high-fat diet fed (HFD) (HFD1a-4a) mice were analyzed on one chip (Chip-A). 4 HFD mice (HFD1b-4b) vs 4 HFD-NMN treated mice (NMN1-4) were examined on the other chip (Chip-B).
2011-12-05 | E-GEOD-31647 | biostudies-arrayexpress
Project description:Martin et al. JCI Insigh (2017). Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which increased NAD+ enhances cardiac function are poorly understood. A putative mechanism of NAD+ therapeutic action is via activation of the mitochondrial NAD+-dependent protein deacetylase sirtuin 3 (SIRT3). We assessed the therapeutic efficacy of NMN and the role of SIRT3 in the Friedreich’s Ataxia cardiomyopathy mouse model (FXNKO). At baseline, the FXNKO heart has mitochondrial protein hyperacetylation, reduced Sirt3 mRNA expression, and evidence of increased NAD+ salvage. Remarkably, NMN administered to FXNKO mice restores cardiac function to near-normal levels. To determine whether SIRT3 is required for NMN therapeutic efficacy, we generated SIRT3KO and SIRT3KO/FXNKO (dKO) knockout models. The improvement in cardiac function upon NMN treatment in the FXNKO is lost in the dKO model, demonstrating that the effects of NMN are dependent upon cardiac SIRT3. Coupled with cardio- protection, SIRT3 mediates NMN-induced improvements in both cardiac and extra-cardiac metabolic function and energy metabolism. Taken together, these results serve as important preclinical data for NMN supplementation or SIRT3 activator therapy in Friedreich’s Ataxia patients.
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2016-12-01 | GSE85718 | GEO
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