Abstract
OBJECTIVE: While it is well established that adipose tissue-derived inflammation plays an important role in the pathogenic mechanisms linking obesity with metabolic dysfunction, the inflammatory mediators involved have not been fully elucidated. Here, we explored IL-12 family cytokines with a focus on IL-27 during obesity-induced inflammation in mice and cultured adipocytes (ADs) following exposure to inflammatory stimuli. METHODS: Relative mRNA abundance of IL-12 cytokines was assessed by reverse transcription polymerase chain reaction (RT-PCR) in genetically obese B6-ob/ob mice as well as C57BL/6J mice fed a high-fat diet and in ADs following exposure to inflammatory stimuli. Protein secretion of cytokines into culture media was assessed by ELISA, and the biological outcome of IL-27 stimulation was assessed by RT-PCR and immunoblotting. RESULTS: Heterodimeric subunits constituting IL-27 were significantly induced in obese mice. While all IL-12 genes were markedly induced by inflammatory stress in cultured ADs, IL-27 protein was the only cytokine secreted into culture media in response to inflammatory stress. Cultured ADs also responded to IL-27 stimulation with divergent outcomes that were dependent on the inflammatory milieu of target cells. CONCLUSIONS: These findings support the premise of autocrine/paracrine mechanisms involving IL-27 in ADs under conditions of inflammatory stress that may link obesity with inflammatory diseases.