Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration.

Nicotinamide riboside kinases (NRKs) control the conversion of dietary Nicotinamide Riboside (NR) to NAD, but little is known about their contribution to endogenous NAD turnover and muscle plasticity during skeletal muscle growth and remodeling. Using NRK1/2 double KO (NRKdKO) mice, we investigated the influence of NRKs on NAD metabolism and muscle homeostasis, and on the response to neurogenic muscle atrophy and regeneration following muscle injury. Muscles from NRKdKO animals have altered nicotinamide (NAM) salvage and a decrease in mitochondrial content.

Metabolomics: Going Deeper, Going Broader, Going Further.

Metabolomics is a continuously dynamic field of research that is driven by demanding research questions and technological advances alike. In this review we highlight selected recent and ongoing developments in the area of mass spectrometry-based metabolomics. The field of view that can be seen through the metabolomics lens can be broadened by adoption of separation techniques such as hydrophilic interaction chromatography and ion mobility mass spectrometry (going broader).

Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD by Generating Dihydronicotinamide Riboside.

Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD precursors influence intracellular NAD levels.

Studying Metabolism by NMR-Based Metabolomics.

During the past few decades, the direct analysis of metabolic intermediates in biological samples has greatly improved the understanding of metabolic processes. The most used technologies for these advances have been mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. NMR is traditionally used to elucidate molecular structures and has now been extended to the analysis of complex mixtures, as biological samples: NMR-based metabolomics.

A Method to Monitor the NAD Metabolome-From Mechanistic to Clinical Applications.

Nicotinamide adenine dinucleotide (NAD) and its reduced form (NADH) are coenzymes employed in hundreds of metabolic reactions. NAD also serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and ADP-ribosyl cyclases. Given the pivotal role of NAD(H) in health and disease, studying NAD metabolism has become essential to monitor genetic- and/or drug-induced perturbations related to metabolic status and diseases (such as ageing, cancer or obesity), and its possible therapies.

Contribution of genetic ancestry and polygenic risk score in meeting vitamin B12 needs in healthy Brazilian children and adolescents.

Polymorphisms in genes related to the metabolism of vitamin B12 haven't been examined in a Brazilian population. To (a) determine the correlation between the local genetic ancestry components and vitamin B12 levels using ninety B12-related genes; (b) determine associations between these genes and their SNPs with vitamin B12 levels; (c) determine a polygenic risk score (PRS) using significant variants. This cross-sectional study included 168 children and adolescents, aged 9-13 years old.

Network medicine framework shows that proximity of polyphenol targets and disease proteins predicts therapeutic effects of polyphenols.

Polyphenols, natural products present in plant-based foods, play a protective role against several complex diseases through their antioxidant activity and by diverse molecular mechanisms. Here we develop a network medicine framework to uncover mechanisms for the effects of polyphenols on health by considering the molecular interactions between polyphenol protein targets and proteins associated with diseases. We find that the protein targets of polyphenols cluster in specific neighbourhoods of the human interactome, whose network proximity to disease proteins is predictive of the molecule's known therapeutic effects.

Metabolic Groups Related to Blood Vitamin Levels and Inflammatory Biomarkers in Brazilian Children and Adolescents.

Certain B-vitamins and vitamin A may be involved in inflammatory pathways associated with homocysteine and omega-3 fatty acids. The aims of this study were (i) to determine whether different metabolic profiles of B-vitamins and vitamin A in Brazilian children and adolescents were positively or negatively related to homocysteine and omega-3 fatty acids using k-means clustering analysis, (ii) compare nutrient intakes and metabolites between the different metabolic profiles, (iii) evaluate if the statistically significant metabolites found between the metabolic groups, can predict the variation of leukotriene A4 hydrolase (LTA4H) levels, a biomarker of low-grade inflammation, in the total studied population. This cross-sectional study included 124 children and adolescents, aged 9-13 y old.

SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease.

Mitochondrial acyl-coenzyme A species are emerging as important sources of protein modification and damage. Succinyl-CoA ligase (SCL) deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. Here, we show that succinyl-CoA accumulates in cells derived from patients with recessive mutations in the tricarboxylic acid cycle (TCA) gene succinyl-CoA ligase subunit-β (SUCLA2), causing global protein hyper-succinylation.

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.

Aims/hypothesis: In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress.

Methods: Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.

Biomarker-based validity of a food frequency questionnaire estimating intake in Brazilian children and adolescents.

This study evaluated the validity of nutrient and food group intakes estimated by an FFQ against biomarkers. A 71-item semiquantitative FFQ was administered to 210 Brazilian children and adolescents aged 9-13 years. Intakes were correlated with biomarkers in plasma and red blood cells.

DNA damage is inversely associated to blood levels of DHA and EPA fatty acids in Brazilian children and adolescents.

This study aimed to investigate the association between DNA damage and blood levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), retinol, beta-carotene and riboflavin in Brazilian children and adolescents. Subjects (n = 140) were healthy boys and girls aged 9 to 13 years in Ribeirão Preto (SP, Brazil). Data collection included anthropometry, assessment of energy intake and blood sampling.

Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

Background: Constitutional thinness (CT), a non-malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free-living state. Weight and metabolic responses to protein caloric supplementation has not been yet explored in CT.

Metabo groups in response to micronutrient intervention: Pilot study.

Micronutrients and their metabolites are cofactors in proteins involved in lipid metabolism. The present study was a subproject of the Harmonized Micronutrient Project (ClinTrials.gov # NCT01823744).

AlpsNMR: an R package for signal processing of fully untargeted NMR-based metabolomics.

Summary: Nuclear magnetic resonance (NMR)-based metabolomics is widely used to obtain metabolic fingerprints of biological systems. While targeted workflows require previous knowledge of metabolites, prior to statistical analysis, untargeted approaches remain a challenge. Computational tools dealing with fully untargeted NMR-based metabolomics are still scarce or not user-friendly.

Vitamin B2 and Folate Concentrations are Associated with ARA, EPA and DHA Fatty Acids in Red Blood Cells of Brazilian Children and Adolescents.

Vitamins B2, B6, B12, and folate are essential for methylation reactions and possibly influence the transport of polyunsaturated fatty acids in plasma and red blood cells (RBC). Associations between B-vitamin biomarkers and fatty acid (FA) profile were analyzed in Brazilian children and adolescents. This cross-sectional study included 249 children and adolescents, aged 9-13 years old.

A reduced form of nicotinamide riboside defines a new path for NAD biosynthesis and acts as an orally bioavailable NAD precursor.

Objective: A decay in intracellular NAD levels is one of the hallmarks of physiological decline in normal tissue functions. Accordingly, dietary supplementation with NAD precursors can prevent, alleviate, or even reverse multiple metabolic complications and age-related disorders in diverse model organisms. Within the constellation of NAD precursors, nicotinamide riboside (NR) has gained attention due to its potent NAD biosynthetic effects in vivo while lacking adverse clinical effects.

Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage.

Supplementation with the NAD precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD synthesis in hepatic cells.

Factors affecting intake, metabolism and health benefits of phenolic acids: do we understand individual variability?

Introduction: Phenolic acids are important phenolic compounds widespread in foods, contributing to nutritional and organoleptic properties.

Factors Affceting Individual Variability: The bioavailability of these compounds depends on their free or conjugated presence in food matrices, which is also affected by food processing. Phenolic acids undergo metabolism by the host and residing intestinal microbiota, which causes conjugations and structural modifications of the compounds.