Background

Oncostatin M (OSM) is a cytokine that plays a key role in inflammation. The contribution of OSM to the inflammatory state during obesity is not fully understood. We evaluated the levels of OSM in patients with obesity and altered glucose homeostasis. In addition, we examined the effects of OSM on human adipocytes and assessed whether OSM immunoneutralization could revert metabolic impairments caused by a high-fat diet (HFD) in mice.

Methods

28 patients with severe obesity were included in this study and stratified according into two groups by glycemia status:normoglycemics and hyperglycemics. Subcutaneous and visceral white adipose tissue were obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response. Finally, HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects.

Results

OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated inversely with Glut4 mRNA levels, and directly with insulin levels, HOMA-IR, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor KO mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from mice fed a HFD.

Conclusions

OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.