Heesun Nam1, Bradley S Ferguson1, Jacqueline M Stephens2, Ron F Morrison1. 1. Department of Nutrition, the University of North Carolina at Greensboro, Greensboro, North Carolina, USA. 2. Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
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.
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 obesemice. 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.
Authors: Zhiping Li; Jude A Oben; Shiqi Yang; Huizhi Lin; Elizabeth A Stafford; Mark J Soloski; Steven A Thomas; Anna Mae Diehl Journal: Hepatology Date: 2004-08 Impact factor: 17.425
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