Intracellular levels of NAD regulate metabolism, among other ways, through enzymes that use NAD as a substrate, capable of inducing catabolic processes, such as lipid oxidation, glucose uptake, and mitochondrial activity. In several model organisms, administering precursor compounds for NAD synthesis increases its levels, improves lipid and glucose homeostasis, and reduces weight gain. However, evidence of the effects of these precursors on human patients needs to be better evaluated. Therefore, we carried out a systematic review and meta-analysis of randomized clinical trials that assessed the effects of NAD precursors on Metabolic Syndrome parameters in humans. We based our methods on PRISMA 2020. Our search retrieved 429 articles, and 19 randomized controlled trials were included in the meta-analysis. We assessed the risk of bias with the Rob 2 algorithm and summarized the quality of evidence with the GRADE algorithm. Supplementation with NAD precursors reduced plasma levels of total cholesterol and triglycerides in volunteers, but the intervention did not significantly affect the other outcomes analyzed. Three of the included articles presented a high risk of bias. The quality of evidence varied between very low and low due to the risk of bias, imprecision, and indirectness. The number of participants in outcomes other than lipidemia is still generally tiny; therefore, more clinical trials evaluating these parameters will increase the quality of the evidence. On the other hand, quality randomized studies are essential to assess better the effects of NAD precursors on lipidemia.
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http://dx.doi.org/10.1055/a-2382-6829 | DOI Listing |
Nat Metab
January 2025
Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Third Hospital of Shanxi Medical University, the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province, Taiyuan, China.
Skeletal muscle is a critical organ in maintaining homoeostasis against metabolic stress, and histone post-translational modifications are pivotal in those processes. However, the intricate nature of histone methylation in skeletal muscle and its impact on metabolic homoeostasis have yet to be elucidated. Here, we report that mitochondria-rich slow-twitch myofibers are characterized by significantly higher levels of H3K36me2 along with repressed expression of Kdm2a, an enzyme that specifically catalyses H3K36me2 demethylation.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Iron-sulfur clusters are essential metallocofactors synthesized by multiprotein machineries via an unclear multistep process. Here we report a step-by-step dissection of the [2Fe-2S] cluster assembly process by the Escherichia coli iron-sulfur cluster (ISC) assembly machinery using an in vitro reconstituted system and a combination of biochemical and spectroscopic techniques. We show that this process is initiated by iron binding to the scaffold protein IscU, which triggers persulfide insertion by the cysteine desulfurase IscS upon the formation of a complex with IscU.
View Article and Find Full Text PDFSci Rep
January 2025
Shenyang Institute of Computing Technology, Chinese Academy of Sciences, Shenyang, 110168, Liaoning, China.
The problem of ground-level ozone (O) pollution has become a global environmental challenge with far-reaching impacts on public health and ecosystems. Effective control of ozone pollution still faces complex challenges from factors such as complex precursor interactions, variable meteorological conditions and atmospheric chemical processes. To address this problem, a convolutional neural network (CNN) model combining the improved particle swarm optimization (IPSO) algorithm and SHAP analysis, called SHAP-IPSO-CNN, is developed in this study, aiming to reveal the key factors affecting ground-level ozone pollution and their interaction mechanisms.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biochemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
Antibiotic-resistant strains of Staphylococcus aureus pose a significant threat in healthcare, demanding urgent therapeutic solutions. Combining bacteriophages with conventional antibiotics, an innovative approach termed phage-antibiotic synergy, presents a promising treatment avenue. However, to enable new treatment strategies, there is a pressing need for methods to assess their efficacy reliably and rapidly.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
Tambjamines are complex bipyrrole-containing natural products that possess promising bioactive properties. Although is known to produce both cyclic tambjamine MYP1 and the linear precursor (YP1), the biosynthetic machinery used to catalyze the site-selective oxidative carbocyclization at the unactivated 1° carbon of YP1 has remained unclear. Here, we demonstrate that a three-component Rieske system consisting of an oxygenase (TamC) and two redox partner proteins is responsible for this unprecedented activity on YP1 and potentially, a non-native substrate (BE-18591).
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