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

Abstract

Objective: This study examined the phenotypic effects of adipocyte-specific oncostatin M receptor (OSMR) loss in chow-fed mice.

Methods: 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.

Results: 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.

Conclusions: 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.