Di Francesco, AndreaChoi, YoungshimBernier, MichelZhang, YingchunDiaz-Ruiz, AlbertoAon, Miguel A.Kalafut, KrystleEhrlich, Margaux R.Murt, KelseyAli, AhmedPearson, Kevin J.Levan, SophiePreston, Joshua D.Martin-Montalvo, AlejandroMartindale, Jennifer L.Abdelmohsen, KotbMichel, Cole R.Willmes, Diana M.Henke, ChristineNavas, PlacidoVillalba, Jose ManuelSiegel, DavidGorospe, MyriamFritz, KristoferBiswal, ShyamRoss, Davidde Cabo, Rafael2022-07-222022-07-222020-11-19Di Francesco A, Choi Y, Bernier M, Zhang Y, Diaz-Ruiz A, Aon MA, et al. NQO1 protects obese mice through improvements in glucose and lipid metabolism. NPJ Aging Mech Dis. 2020 Nov 19;6(1):13http://hdl.handle.net/10668/3814Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD+ metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Insulin resistanceMiceMetabolismNF-E2-related factor 2RNAGlucoseResistencia a la insulinaRatonesMetabolismoFactor 2 relacionado con NF-E2ARNMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::MetabolismMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin ResistanceMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Basic-Leucine Zipper Transcription Factors::NF-E2-Related Factor 2Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::GlucoseMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-FatMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Sirtuins::Sirtuin 3Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Acylation::AcetylationMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose TissueMedical Subject Headings::Anatomy::Tissues::Muscles::Muscle, Striated::Muscle, SkeletalMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::HomeostasisMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Energy Metabolism::Oxidation-ReductionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Transfer TechniquesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotyperesearch article33298924Acceso abierto10.1038/s41514-020-00051-62056-39733