Oncostatin M in the development of metabolic syndrome and its potential as a novel therapeutic target.

Oncostatin M (OSM), a member of the IL-6 family of cytokines, plays an important role in various biologic actions, including cell growth, neuronal development, and inflammatory responses. Recently, we demonstrated the unique relationship between OSM and metabolic syndrome in mice. Mice lacking OSM receptor ß subunit (OSMRß-/- mice) exhibited late-onset obesity. Before the onset of obesity, adipose tissue inflammation and insulin resistance were observed in OSMRß-/- mice. In addition, high-fat diet-induced metabolic disorders, including obesity, adipose tissue inflammation, insulin resistance, and hepatic steatosis, were aggravated in OSMRß-/- mice compared to those in wild-type mice. Consistent with these findings, OSM treatment dramatically improved these metabolic disorders in the mouse model of metabolic syndrome. Interestingly, OSM directly changed the phenotypes of adipose tissue macrophages toward anti-inflammatory M2 type. Furthermore, fatty acid content in the hepatocytes was decreased by OSM through expression regulation of several key enzymes of hepatic lipid metabolism. These findings suggest that OSM is a novel therapeutic target for metabolic syndrome.