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Regulation of obesity and fatty acid-induced inflammation by AMP-activated protein kinase in obese/type 2 diabetic and inactive human skeletal muscle (AMPKANTIINFLAMMATION)
Date du début: 8 juil. 2011, Date de fin: 7 janv. 2013 PROJET  TERMINÉ 

It is increasingly recognised that obesity is characterised by chronic activation of inflammatory pathways in skeletal muscle and that this is a causative factor of obesity associated insulin resistance; also contributing to the pathogenesis of complications of diabetes. My work has shown that activation of AMP-activated protein kinase (AMPK) can regulate inflammatory signalling by antagonising fatty acid-induced NFκB and MAPK signalling (Green CJ et al., in preparation). The latter work was carried out in rat (L6) muscle cells, this project will confirm whether AMPK can regulate fatty acid/obesity-induced inflammatory signalling in human skeletal muscle cells from obese patients and assess to what extent pharmacological activation of AMPK can be utilised in humans to treat fatty acid-induced inflammation. The overall objectives of this project are to demonstrate that; 1) Isolated, cultured, skeletal muscle myocytes from obese patients retain their inflammatory phenotype as seen in vivo, 2) AMPK activating drugs can antagonise obesity associated inflammation in isolated skeletal muscle myocytes from obese, type 2 diabetic subjects, 3) to assess whether physical inactivity renders isolated skeletal muscle more susceptible to fatty acid-induced inflammation compared to healthy controls, and 4) to provide evidence that activation of AMPK, using insulin sensitising agents, can be used as an effective strategy to ameliorate obesity associated inflammation in humans at the whole body level.

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