Reductive stress—a common metabolic feature of obesity and cancer

Reductive stress, characterized by rising level of NADH (nicotinamide adenine dinucleotide) for a status of NADH/NAD+ ratio elevation, has been reported in obesity and cancer. However, the mechanism and significance of reductive stress remain to be established in obesity. This perspective is prepare...

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Main Authors: Man Luo, Xiwen Ma, Jianping Ye
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Acta Pharmaceutica Sinica B
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211383524003472
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author Man Luo
Xiwen Ma
Jianping Ye
author_facet Man Luo
Xiwen Ma
Jianping Ye
author_sort Man Luo
collection DOAJ
description Reductive stress, characterized by rising level of NADH (nicotinamide adenine dinucleotide) for a status of NADH/NAD+ ratio elevation, has been reported in obesity and cancer. However, the mechanism and significance of reductive stress remain to be established in obesity. This perspective is prepared to address the issue with new insights published recently. NADH is used in production of NADPH, glutathione, ATP and heat in the classical biochemistry. In obesity, elevation of NADH/NAD+ ratio, likely from overproduction due to substrate overloading, has been found in the liver for insulin resistance and gluconeogenesis. New evidence demonstrates that the elevation may induce lipogenesis, purine biosynthesis and gluconeogenesis through activation of transcription factors of ChREBP and NRF2. In cancer cells, NADH/NAD+ elevation under the Warburg effect is primarily derived from decreased NADH consumption in the mitochondrial respiration. Alternatively, NRF2 overactivation from gene mutation represents another mechanism of NADH/NAD+ elevation from NADH production in the cancer cells. The elevation is required for quick proliferation of cancer cells through induction of biosynthesis of the essential molecules. It appears that the causes of reductive stress are different between obesity and cancer, while its impact in anabolism is similar in the two conditions.
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spelling doaj-art-14d4efde1e4e4d63bbd0eaa2be28534f2024-12-18T08:48:45ZengElsevierActa Pharmaceutica Sinica B2211-38352024-12-01141251815185Reductive stress—a common metabolic feature of obesity and cancerMan Luo0Xiwen Ma1Jianping Ye2Metabolic Disease Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450052, ChinaMetabolic Disease Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450052, China; Institute of Trauma and Metabolism, Zhengzhou University, Zhengzhou 450052, ChinaMetabolic Disease Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450052, China; Institute of Trauma and Metabolism, Zhengzhou University, Zhengzhou 450052, China; Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; Zhengzhou Key laboratory of Obesity Research, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450052, China; Corresponding author.Reductive stress, characterized by rising level of NADH (nicotinamide adenine dinucleotide) for a status of NADH/NAD+ ratio elevation, has been reported in obesity and cancer. However, the mechanism and significance of reductive stress remain to be established in obesity. This perspective is prepared to address the issue with new insights published recently. NADH is used in production of NADPH, glutathione, ATP and heat in the classical biochemistry. In obesity, elevation of NADH/NAD+ ratio, likely from overproduction due to substrate overloading, has been found in the liver for insulin resistance and gluconeogenesis. New evidence demonstrates that the elevation may induce lipogenesis, purine biosynthesis and gluconeogenesis through activation of transcription factors of ChREBP and NRF2. In cancer cells, NADH/NAD+ elevation under the Warburg effect is primarily derived from decreased NADH consumption in the mitochondrial respiration. Alternatively, NRF2 overactivation from gene mutation represents another mechanism of NADH/NAD+ elevation from NADH production in the cancer cells. The elevation is required for quick proliferation of cancer cells through induction of biosynthesis of the essential molecules. It appears that the causes of reductive stress are different between obesity and cancer, while its impact in anabolism is similar in the two conditions.http://www.sciencedirect.com/science/article/pii/S2211383524003472Reductive stressNADHCancerObesityGluconeogenesisLipogenesis
spellingShingle Man Luo
Xiwen Ma
Jianping Ye
Reductive stress—a common metabolic feature of obesity and cancer
Acta Pharmaceutica Sinica B
Reductive stress
NADH
Cancer
Obesity
Gluconeogenesis
Lipogenesis
title Reductive stress—a common metabolic feature of obesity and cancer
title_full Reductive stress—a common metabolic feature of obesity and cancer
title_fullStr Reductive stress—a common metabolic feature of obesity and cancer
title_full_unstemmed Reductive stress—a common metabolic feature of obesity and cancer
title_short Reductive stress—a common metabolic feature of obesity and cancer
title_sort reductive stress a common metabolic feature of obesity and cancer
topic Reductive stress
NADH
Cancer
Obesity
Gluconeogenesis
Lipogenesis
url http://www.sciencedirect.com/science/article/pii/S2211383524003472
work_keys_str_mv AT manluo reductivestressacommonmetabolicfeatureofobesityandcancer
AT xiwenma reductivestressacommonmetabolicfeatureofobesityandcancer
AT jianpingye reductivestressacommonmetabolicfeatureofobesityandcancer