%0 Journal Article
%A Di Francesco, Andrea
%A Choi, Youngshim
%A Bernier, Michel
%A Zhang, Yingchun
%A Diaz-Ruiz, Alberto
%A Aon, Miguel A.
%A Kalafut, Krystle
%A Ehrlich, Margaux R.
%A Murt, Kelsey
%A Ali, Ahmed
%A Pearson, Kevin J.
%A Levan, Sophie
%A Preston, Joshua D.
%A Martin-Montalvo, Alejandro
%A Martindale, Jennifer L.
%A Abdelmohsen, Kotb
%A Michel, Cole R.
%A Willmes, Diana M.
%A Henke, Christine
%A Navas, Placido
%A Villalba, Jose Manuel
%A Siegel, David
%A Gorospe, Myriam
%A Fritz, Kristofer
%A Biswal, Shyam
%A Ross, David
%A de Cabo, Rafael
%T NQO1 protects obese mice through improvements in glucose and lipid metabolism
%D 2020
%U http://hdl.handle.net/10668/3814
%X Chronic 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.
%K Insulin resistance
%K Mice
%K Metabolism
%K NF-E2-related factor 2
%K RNA
%K Glucose
%K Resistencia a la insulina
%K Ratones
%K Metabolismo
%K Factor 2 relacionado con NF-E2
%K ARN
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