Molecular Mechanisms of Obesity-Associated Oxidative Stress and Therapeutic Strategies

Obesity is a chronic metabolic disorder characterized by excessive adipose tissue accumulation and associated with systemic oxidative stress, mitochondrial dysfunction, and chronic low-grade inflammation. Adipose tissue dysfunction promotes the overproduction of reactive oxygen species through multiple mechanisms, including NADPH oxidase activation, mitochondrial electron transport chain leakage, and endoplasmic reticulum stress via mitochondria-associated ER membranes. The resulting oxidative stress damages lipids, proteins, and DNA, while activating redox-sensitive signaling pathways that perpetuate inflammation and insulin resistance. Moreover, obesity impairs endogenous antioxidant defense systems, including reduced activity of superoxide dismutase, glutathione peroxidase, and catalase, as well as magnesium deficiency that compromises glutathione synthesis. This review synthesizes current knowledge of molecular mechanisms linking obesity to oxidative stress and discusses key biomarker categories, including lipid peroxidation products, protein oxidation markers, DNA damage markers, adipokine ratios, and microRNAs. We also evaluate therapeutic strategies targeting obesity-associated oxidative stress, with emphasis on lifestyle interventions, pharmacological agents, and dietary compounds including resveratrol, curcumin, lycopene, and astaxanthin. Understanding the relationship between obesity and oxidative stress is essential for developing mechanism-directed therapeutic interventions.