The role of carbon monoxide in metabolic disease.

Metabolic disease is a complex disorder defined by various factors that increase the risk of cardiovascular disease and type 2 diabetes mellitus. In recent years, the incidence of chronic metabolic disease has dramatically increased throughout the world. These chronic metabolic diseases are associated with elevated inflammatory activities. In addition, endoplasmic reticulum (ER) stress leads to metabolic syndrome. Inflammation and ER stress are linked in the context of metabolic homeostasis and disease. Carbon monoxide (CO), a reaction product of heme oxygenase-1 (HO-1), reduces oxidative stress and inflammatory response and protects cells from ER stress. CO has anti-inflammatory effects via induction of HO-1 expression and prevents ER stress-induced apoptosis by inhibiting the C/EBP homologous protein expression. In addition to its anti-inflammatory effects and antiapoptotic effects, HO-1 plays an important role in insulin release and glucose metabolism. In our study, inhalation of CO gas or CO-releasing molecule injection ameliorates 30% fructose or methionine-deficient- and choline-deficient-diet-induced hepatic steatosis. Therefore, CO can be studied in the search for potential therapeutic targets for metabolic diseases via inhibition of inflammatory response and ER stress.