Abstract

Obesity has emerged as a global health crisis, intricately linked to the pathogenesis of type 2 diabetes mellitus 
(T2DM) and various malignancies. Central to this pathological nexus is the interplay between oxidative stress 
and mitochondrial dysfunction. Adipose tissue expansion in obesity induces chronic inflammation, leading to 
the overproduction of reactive oxygen species (ROS) and impairment of mitochondrial function. This redox 
imbalance disrupts insulin signaling, impairs glucose homeostasis, and fosters a metabolic environment 
conducive to DNA damage, mutagenesis, and cancer development. Moreover, mitochondrial dysfunction 
exacerbates adipocyte insulin resistance and contributes to the metabolic reprogramming characteristic of 
cancer cells. This review critically examines the molecular and biochemical mechanisms by which oxidative 
stress and mitochondrial dysfunction bridge obesity to both diabetes and carcinogenesis. We explore the roles 
of key mediators such as NADPH oxidase, mitochondrial respiratory chain complexes, and redox-sensitive 
transcription factors, including NF-κB and HIF-1α. Understanding these interconnected pathways opens 
avenues for novel therapeutic strategies targeting redox homeostasis and mitochondrial health to mitigate 
obesity-driven metabolic diseases and cancer progression.