Gp130 Cytokines Exert Differential Patterns of Crosstalk in Adipocytes Both In Vitro and In Vivo

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Glycoprotein 130 (Gp130) cytokines are involved in the regulation of numerous biological processes, including hematopoiesis, immune response, inflammation, cardiovascular action, and neuronal survival. These cytokines share gp130 as a common signal transducer in their receptor complex and typically activate signal transducer and activator of transcription (STAT) 3. Studies have shown that several gp130 cytokines have differential effects on both adipogenesis and insulin-stimulated glucose uptake. Yet, the complex interactions of these cytokines in adipose tissue have not been studied. Gp130 cytokines are differentially regulated in multiple tissues due to the presence of additional receptor components that are required for signaling, including the leukemia inhibitory factor receptor (LIFR). Previous studies from our laboratory highlighted the ability of specific gp130 cytokines to crosstalk in adipocytes that correlated with LIFR degradation. Crosstalk is defined as the ability of one cytokine to modulate the signaling of another cytokine. Our novel studies reveal that white adipose tissue is highly responsive to gp130 cytokines, and we provide the first evidence that these cytokines can exert inhibitory crosstalk in adipose tissue in vivo. Moreover, several gp130 cytokines that use the LIFR, including cardiotrophin-1 (CT-1), LIF, and human oncostatin M (hOSM), can alter the subsequent signaling of other family members in adipocytes both in vitro and in vivo. Our data also show that murine OSM and neuropoietin do not crosstalk in the same manner as other gp130 cytokines, which likely results from their inability to activate the LIFR. Overall, we have observed distinctive patterns of crosstalk signaling by gp130 cytokines in adipocytes in vitro and in vivo and demonstrate the crosstalk is not dependent on new protein synthesis or extracellular-signal-regulated kinase activation.