What is obesity?

Obesity is a medical condition characterized by the excessive accumulation of body fat, to the extent that it may have adverse effects on health. It is commonly assessed using the body mass index (BMI), which is calculated by dividing a person’s weight in kilograms by the square of their height in meters (kg/m^2). A BMI of 30 or higher is typically considered indicative of obesity.


What is the relationship between obesity and oxidative stress?

The relationship between obesity and oxidative stress is significant and plays a central role in the pathogenesis of obesity-related complications. Here’s how obesity and oxidative stress are interconnected:


  • Adipose Tissue Dysfunction: In obesity, there is an abnormal accumulation of adipose (fat) tissue, particularly visceral adipose tissue surrounding internal organs. Adipose tissue dysfunction is characterized by adipocyte hypertrophy (enlargement) and adipose tissue inflammation, which contribute to increased production of pro-inflammatory cytokines and chemokines. This chronic low-grade inflammation promotes oxidative stress by stimulating the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) within adipocytes and immune cells.


  • Mitochondrial Dysfunction: Mitochondria, the cellular organelles responsible for energy production, play a critical role in obesity-related oxidative stress. In obese individuals, mitochondrial dysfunction is commonly observed in adipose tissue, liver, skeletal muscle, and other tissues. Dysfunction of mitochondria leads to impaired energy metabolism, increased ROS production, and oxidative stress. Oxidative damage to mitochondrial DNA, proteins, and lipids further exacerbates mitochondrial dysfunction and contributes to insulin resistance and other metabolic abnormalities associated with obesity.


  • Insulin Resistance: Obesity is often accompanied by insulin resistance, a condition in which cells become less responsive to the effects of insulin, leading to impaired glucose uptake and metabolism. Insulin resistance is associated with increased oxidative stress and impaired antioxidant defense mechanisms. ROS can interfere with insulin signaling pathways and exacerbate insulin resistance, leading to further lipid accumulation and oxidative stress.


  • Endoplasmic Reticulum Stress: Obesity-related metabolic overload can lead to endoplasmic reticulum (ER) stress, a condition in which protein folding and processing within the ER are disrupted. ER stress activates inflammatory pathways and induces oxidative stress through the production of ROS by the ER-resident enzyme NADPH oxidase 4 (NOX4). Oxidative stress further exacerbates ER stress, forming a vicious cycle that contributes to adipocyte dysfunction, insulin resistance, and inflammation in obesity.


  • Antioxidant Defense Mechanisms: To counteract the harmful effects of oxidative stress, cells have antioxidant defense mechanisms that scavenge ROS and protect against oxidative damage. However, in obesity, the balance between ROS production and antioxidant defenses is disrupted, leading to oxidative stress overload. Reduced levels of antioxidants, such as glutathione and superoxide dismutase, have been observed in obese individuals, further exacerbating oxidative damage and metabolic dysfunction.


Overall, oxidative stress is a central mechanism in the pathogenesis of obesity-related complications, including insulin resistance, inflammation, dyslipidemia, cardiovascular disease, and non-alcoholic fatty liver disease.