Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome

The global epidemic of obesity continues unabated with sequelae of diabetes and metabolic syndrome. This review reflects the dramatic increase in research on the role of increased expression of heme oxygenase (HO)-1/HO-2, biliverdin reductase, and HO activity on vascular disease. The HO system engages with other systems to mitigate the deleterious effects of oxidative stress in obesity and cardiovascular disease (CVD). Recent reports indicate that HO-1/HO-2 protein expression and HO activity have several important roles in hemostasis and reactive oxygen species (ROS)-dependent perturbations associated with metabolic syndrome. HO-1 protects tissue during inflammatory stress in obesity through the degradation of pro-oxidant heme and the production of carbon monoxide (CO) and bilirubin, both of which have anti-inflammatory and anti-apoptotic properties. By contrast, repression of HO-1 is associated with increases of cellular heme and inflammatory conditions including hypertension, stroke, and atherosclerosis. HO-1 is a major focus in the development of potential therapeutic strategies to reverse the clinical complications of obesity and metabolic syndrome.

TrendsObesity is a major risk factor in the development of diabetes, hypertension, fatty liver, and CVD.HO-1 and HO-2 catalyze the breakdown of heme, a potentially harmful pro-oxidant, into potent anti-oxidants such as biliverdin/bilirubin and CO, with an anti-inflammatory effect.This is the first review to discuss translational research that summarizes human genetic polymorphism of HO-1 and the effectiveness of bilirubin to ameliorate CVD.This review uncovers a mechanistic link between obesity and the vascular system, and provides a conceptual basis for developing new drugs for the management of metabolic syndrome.We provide a conceptual basis for the development of new therapeutic strategies that target HO-1 and biliverdin to ameliorate obesity, adipocyte (fat stem cell) dysfunction, and vascular dysfunction associated with the metabolic syndrome.