RT Journal Article
T1 NQO1 protects obese mice through improvements in glucose and lipid metabolism
A1 Di Francesco, Andrea
A1 Choi, Youngshim
A1 Bernier, Michel
A1 Zhang, Yingchun
A1 Diaz-Ruiz, Alberto
A1 Aon, Miguel A.
A1 Kalafut, Krystle
A1 Ehrlich, Margaux R.
A1 Murt, Kelsey
A1 Ali, Ahmed
A1 Pearson, Kevin J.
A1 Levan, Sophie
A1 Preston, Joshua D.
A1 Martin-Montalvo, Alejandro
A1 Martindale, Jennifer L.
A1 Abdelmohsen, Kotb
A1 Michel, Cole R.
A1 Willmes, Diana M.
A1 Henke, Christine
A1 Navas, Placido
A1 Villalba, Jose Manuel
A1 Siegel, David
A1 Gorospe, Myriam
A1 Fritz, Kristofer
A1 Biswal, Shyam
A1 Ross, David
A1 de Cabo, Rafael
K1 Insulin resistance
K1 Mice
K1 Metabolism
K1 NF-E2-related factor 2
K1 RNA
K1 Glucose
K1 Resistencia a la insulina
K1 Ratones
K1 Metabolismo
K1 Factor 2 relacionado con NF-E2
K1 ARN
AB 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.
PB Springer Nature
YR 2020
FD 2020-11-19
LK http://hdl.handle.net/10668/3814
UL http://hdl.handle.net/10668/3814
LA en
NO Di 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):13
DS RISalud
RD Apr 7, 2025