Adipose Tissue Dysfunction Occurs Independently of Obesity in Adipocyte-Specific Oncostatin Receptor Knockout Mice.

Abstract

This study examined the phenotypic effects of adipocyte-specific oncostatin M receptor (OSMR) loss in chow-fed mice. Chow-fed adipocyte-specific OSMR knockout (FKO) mice and littermate OSMR^fl/fl controls were studied. Tissue weights, insulin sensitivity, adipokine production, and stromal cell immunophenotypes were assessed in epididymal fat (eWAT); serum adipokine production was also assessed. In vitro, adipocytes were treated with oncostatin M, and adipokine gene expression was assessed. Body weights, fasting blood glucose levels, and eWAT weights did not differ between genotypes. However, the eWAT of OSMR^FKO mice was modestly less responsive to insulin stimulation than that of OSMR^fl/fl mice. Notably, significant increases in adipokines, including C-reactive protein, lipocalin 2, intercellular adhesion molecule-1, and insulinlike growth factor binding protein 6, were observed in the eWAT of OSMR^FKO mice. In addition, significant increases in fetuin A and intercellular adhesion molecule-1 were detected in OSMR^FKO serum. Flow cytometry revealed a significant increase in leukocyte number and modest, but not statistically significant, increases in B cells and T cells in the eWAT of OSMR^FKO mice. The chow-fed OSMR^FKO mice exhibited adipose tissue dysfunction and increased proinflammatory adipokine production. These results suggest that intact adipocyte oncostatin M-OSMR signaling is necessary for adipose tissue immune cell homeostasis.