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Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging

Reactive oxygen species (ROS) are produced mainly by mitochondrial respiration and function as signaling molecules in the physiological range. However, ROS production is also associated with the pathogenesis of various diseases, including insulin resistance (IR) and type 2 diabetes (T2D). This revie...

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Detalles Bibliográficos
Autores principales: Kasai, Shuya, Kokubu, Daichi, Mizukami, Hiroki, Itoh, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605809/
https://www.ncbi.nlm.nih.gov/pubmed/37892226
http://dx.doi.org/10.3390/biom13101544
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author Kasai, Shuya
Kokubu, Daichi
Mizukami, Hiroki
Itoh, Ken
author_facet Kasai, Shuya
Kokubu, Daichi
Mizukami, Hiroki
Itoh, Ken
author_sort Kasai, Shuya
collection PubMed
description Reactive oxygen species (ROS) are produced mainly by mitochondrial respiration and function as signaling molecules in the physiological range. However, ROS production is also associated with the pathogenesis of various diseases, including insulin resistance (IR) and type 2 diabetes (T2D). This review focuses on the etiology of IR and early events, especially mitochondrial ROS (mtROS) production in insulin-sensitive tissues. Importantly, IR and/or defective adipogenesis in the white adipose tissues (WAT) is thought to increase free fatty acid and ectopic lipid deposition to develop into systemic IR. Fatty acid and ceramide accumulation mediate coenzyme Q reduction and mtROS production in IR in the skeletal muscle, while coenzyme Q synthesis downregulation is also involved in mtROS production in the WAT. Obesity-related IR is associated with the downregulation of mitochondrial catabolism of branched-chain amino acids (BCAAs) in the WAT, and the accumulation of BCAA and its metabolites as biomarkers in the blood could reliably indicate future T2D. Transcription factor NF-E2-related factor 2 (Nrf2), which regulates antioxidant enzyme expression in response to oxidative stress, is downregulated in insulin-resistant tissues. However, Nrf2 inducers, such as sulforaphane, could restore Nrf2 and target gene expression and attenuate IR in multiple tissues, including the WAT.
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spelling pubmed-106058092023-10-28 Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging Kasai, Shuya Kokubu, Daichi Mizukami, Hiroki Itoh, Ken Biomolecules Review Reactive oxygen species (ROS) are produced mainly by mitochondrial respiration and function as signaling molecules in the physiological range. However, ROS production is also associated with the pathogenesis of various diseases, including insulin resistance (IR) and type 2 diabetes (T2D). This review focuses on the etiology of IR and early events, especially mitochondrial ROS (mtROS) production in insulin-sensitive tissues. Importantly, IR and/or defective adipogenesis in the white adipose tissues (WAT) is thought to increase free fatty acid and ectopic lipid deposition to develop into systemic IR. Fatty acid and ceramide accumulation mediate coenzyme Q reduction and mtROS production in IR in the skeletal muscle, while coenzyme Q synthesis downregulation is also involved in mtROS production in the WAT. Obesity-related IR is associated with the downregulation of mitochondrial catabolism of branched-chain amino acids (BCAAs) in the WAT, and the accumulation of BCAA and its metabolites as biomarkers in the blood could reliably indicate future T2D. Transcription factor NF-E2-related factor 2 (Nrf2), which regulates antioxidant enzyme expression in response to oxidative stress, is downregulated in insulin-resistant tissues. However, Nrf2 inducers, such as sulforaphane, could restore Nrf2 and target gene expression and attenuate IR in multiple tissues, including the WAT. MDPI 2023-10-19 /pmc/articles/PMC10605809/ /pubmed/37892226 http://dx.doi.org/10.3390/biom13101544 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kasai, Shuya
Kokubu, Daichi
Mizukami, Hiroki
Itoh, Ken
Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging
title Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging
title_full Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging
title_fullStr Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging
title_full_unstemmed Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging
title_short Mitochondrial Reactive Oxygen Species, Insulin Resistance, and Nrf2-Mediated Oxidative Stress Response—Toward an Actionable Strategy for Anti-Aging
title_sort mitochondrial reactive oxygen species, insulin resistance, and nrf2-mediated oxidative stress response—toward an actionable strategy for anti-aging
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605809/
https://www.ncbi.nlm.nih.gov/pubmed/37892226
http://dx.doi.org/10.3390/biom13101544
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