Reductive stress: The key pathway in metabolic disorders induced by overnutrition

作者：Shiyi Zhang, Shiyi Zhang, Na Wang, Zhichao Gao, Jia Gao, Xiaohui Wang, Hao Xie, Cong‐Yi Wang, Shu Zhang, Shu Zhang · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.012 · 被引用次数：32 · 研究领域：Adipose Tissue and Metabolism、Diet and metabolism studies、Vitamin C and Antioxidants Research

• Emphasizes the importance of maintaining redox balance for physiological homeostasis, with a focus not only on oxidative stress but also on the significance of reductive stress. • Provides substantial evidence that reductive stress significantly impacts diseases, particularly those related to metabolism and cardiovascular health. • Explores the mechanisms of reductive stress, characterized by an excess of endogenous reductants, and its effects on metabolic and cardiovascular disorders, with a specific focus on the endoplasmic reticulum and mitochondria. • Discusses the relationship between antioxidant supplementation and reductive stress, highlighting potential adverse effects and the need for cautious therapeutic approaches. • The structural basis of reductive stress is the abnormality of protein disulfide bonds. An imbalanced redox environment affects the structure of these bonds, subsequently altering protein structure or function, leading to cellular dysfunction. The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on the concept of oxidative stress, which is involved in the mechanism of almost all diseases. However, robust evidence has highlighted that reductive stress, the other side of the redox spectrum, plays a pivotal role in the development of various diseases, particularly those related to metabolism and cardiovascular health. In this review, we present an extensive array of evidence for the occ...