NQO1 通过改善葡萄糖和脂质代谢保护肥胖小鼠。

IF 5.4 Q1 GERIATRICS & GERONTOLOGY NPJ Aging and Mechanisms of Disease Pub Date : 2020-11-19 DOI:10.1038/s41514-020-00051-6
Andrea Di Francesco, Youngshim Choi, Michel Bernier, Yingchun Zhang, Alberto Diaz-Ruiz, Miguel A Aon, Krystle Kalafut, Margaux R Ehrlich, Kelsey Murt, Ahmed Ali, Kevin J Pearson, Sophie Levan, Joshua D Preston, Alejandro Martin-Montalvo, Jennifer L Martindale, Kotb Abdelmohsen, Cole R Michel, Diana M Willmes, Christine Henke, Placido Navas, Jose Manuel Villalba, David Siegel, Myriam Gorospe, Kristofer Fritz, Shyam Biswal, David Ross, Rafael de Cabo
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引用次数: 0

摘要

长期营养过剩会导致代谢紊乱和胰岛素抵抗。通过激活 Nrf2 激活应激反应途径有助于能量代谢的调节。在这里,诱导性激活小鼠的Nrf2和转基因Nrf2靶点NQO1,通过维持葡萄糖稳态、胰岛素敏感性和脂质处理,改善生理结果,从而保护小鼠免受饮食诱导的代谢缺陷的影响。NQO1-RNA 相互作用介导了 NQO1 转基因小鼠骨骼肌中翻译机制的关联和抑制。摄入高脂饮食的 NQO1-Tg 小鼠的脂肪组织巨噬细胞减少,生脂酶的表达增强,同时循环和肝脏脂质减少。代谢组学数据揭示了葡萄糖处理、细胞氧化还原和 NAD+ 代谢改善的系统代谢特征,而骨骼肌中的无标记定量质谱则揭示了中间代谢核心的 SIRT3 靶点乙酰化模式与饮食和基因型有关。因此,在营养过剩的情况下,NQO1 转基因可保持对健康的益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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NQO1 protects obese mice through improvements in glucose and lipid metabolism.

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.

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来源期刊
NPJ Aging and Mechanisms of Disease
NPJ Aging and Mechanisms of Disease Medicine-Geriatrics and Gerontology
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8 weeks
期刊介绍: npj Aging and Mechanisms of Disease is an online open access journal that provides a forum for the world’s most important research in the fields of aging and aging-related disease. The journal publishes papers from all relevant disciplines, encouraging those that shed light on the mechanisms behind aging and the associated diseases. The journal’s scope includes, but is not restricted to, the following areas (not listed in order of preference): • cellular and molecular mechanisms of aging and aging-related diseases • interventions to affect the process of aging and longevity • homeostatic regulation and aging • age-associated complications • translational research into prevention and treatment of aging-related diseases • mechanistic bases for epidemiological aspects of aging-related disease.
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