Insights and Future Directions
Several possible mechanisms linking obesity to cardiovascular disease are considered to be related to insulin resistance. Several adipokines produced by adipose tissue such as leptin, adiponectin, tumor necrosis factor-α (TNF-α), interleukin-6, resistin, visfatin, and retinol binding protein 4, have been suggested to be associated with insulin resistance. Oxidative stress plays a key role in the pathogenesis of insulin resistance and pancreatic β-cell dysfunction. There is evidence that mitochondrial reactive oxygen species (ROS) overproduction is involved in diabetes and diabetic complications. Increased production of TNF-α has been widely associated with obesity-related insulin resistance and abnormal vascular reactivity, the vasculature being an important target of TNF-α. Mitochondria can be a source of TNF-α-induced ROS production in cells and this may contribute to the pathogenesis of TNF-α-induced insulin resistance. Physical exercise and weight loss alter the blood levels of adipokines, and prolonged regimens of diet and exercise improve insulin sensitivity, type 2 diabetic symptoms, and cardiovascular disease symptoms. This chapter will also consider new drugs and therapies including irisin and fibroblast growth factor 21 which stimulate thermogenesis. Adipokines and adipokine receptors represent potential therapeutic targets to combat obesity-linked diseases characterized by inflammation and insulin resistance.