Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8477165 | Molecular and Cellular Endocrinology | 2014 | 29 Pages |
Abstract
Interleukin-6 (IL-6) induces hepatic inflammation and insulin resistance, and therapeutic strategies to counteract the IL-6 action in liver are of high interest. In this study, we demonstrate that acute treatment with AMP-activated protein kinase (AMPK) agonists AICAR and metformin efficiently repressed IL-6-induced hepatic proinflammatory gene expression and activation of STAT3 in a mouse model of diet-induced type 2 diabetes, bringing it back to basal nonstimulated level. Surprisingly, the inflammatory response in liver induced by IL-6 administration in vivo was markedly blunted in the mice fed a high-fat diet, compared to lean chow-fed controls, while this difference was not replicated in vitro in primary hepatocytes derived from these two groups of mice. In summary, our work reveals that partial hepatic IL-6 resistance develops in the mouse model of type 2 diabetes, while the anti-inflammatory action of AMPK is maintained. Systemic factors, rather than differences in intracellular IL-6 receptor signaling, are likely mediating the relative impairment in IL-6 effect.
Keywords
sgp130SAAgp130SHP2AMPKGTTqRT-PCRSOCS3HRPSoluble gp130IL-6AICARSTAT3Janus kinaseAMP-activated protein kinaseSmall interfering RNAsiRNAinsulin tolerance testinflammationinterleukin-6ITTEnzyme-linked immunosorbent assayELISAglucose tolerance testintraperitonealType 2 diabetesserum amyloid Asuppressor of cytokine signaling 3signal transducer and activator of transcription 3Haptoglobinquantitative real-time PCRHorseradish peroxidaseJAKLiverglycoprotein 130
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Authors
Emmelie Cansby, Annika Nerstedt, Manoj Amrutkar, Esther Nuñez Durán, Ulf Smith, Margit Mahlapuu,