Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases

The recent increase in populations with obesity is a worldwide social problem, and the enhanced susceptibility of obese people to metabolic and cardiovascular diseases has become a growing health threat. An understanding of the molecular basis for obesity-associated disease development is required to prevent these diseases. Many studies have revealed that the mechanism involves various bioactive molecules that are released from adipose tissues and designated as adipocytokines/adipokines. Adiponectin is an adipocytokine that exerts insulin-sensitizing effects in the liver and skeletal muscle via adenosine monophosphate-activated protein kinase and proliferator-activated receptor α activation. Additionally, adiponectin can suppress atherosclerosis development in vascular walls via various anti-inflammatory effects. In contrast, oxidative stress is a harmful factor that systemically increases during obesity and promotes the development of diabetes, atherosclerosis, and various other diseases. In obese mice, oxidative stress is enhanced in adipose tissue before diabetes development, but not in the liver, skeletal muscle, and aorta, suggesting that in obesity, adipose tissue may be a major source of reactive oxygen species (ROS). ROS suppress adiponectin production in adipocytes. Treatment of obese mice with anti-oxidative agents improves insulin resistance and restores adiponectin production. Recent studies have demonstrated that adiponectin protects against oxidative stress-induced damage in the vascular endothelium and myocardium. Thus, decreased circulating adiponectin levels and increased oxidative stress, which are closely linked to each other, should be deeply involved in obesity-associated metabolic and cardiovascular disease pathogenesis.