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

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 (OSM) and adipokine gene expression 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 (ICAM-1), and insulin-like growth factor binding protein 6, were observed in the eWAT of OSMR(FKO) mice. In addition, significant increases in fetuin A and ICAM-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 and T cells in the eWAT of OSMR(FKO) mice. CONCLUSIONS: The chow-fed OSMR(FKO) mouse exhibits adipose tissue dysfunction and increased pro-inflammatory adipokine production. These results suggest that intact adipocyte OSM-OSMR signaling is necessary for adipose tissue immune cell homeostasis.