The TOBI project aims to analyse mechanisms provoking adipokine-mediated crosstalk and an inflammatory drift in obese patients. It will be the remit of this project to develop novel strategies to reduce or reverse major adipokine-mediated adverse interactions in peripheral tissues and by periorganic adipose tissue, namely insulin resistance and vascular dysfunction, respectively. Special attention will be given to the study of novel lipid-derived adipokines and the identification of targets for drug development that could interfere with the obesity-associated inflammatory drift. TOBI research focuses on molecular mechanisms initiating and promoting inflammatory signalling pathways in adipocytes and adipose tissue macrophages that cause a shift to inflammatory adipokines to interfere with insulin sensitivity and vascular function. Adipocyte dysfunction by alterations in ER stress signalling and lipolysis will be analysed as probable starting points of adipocyte inflammatory alterations. Signalling pathways and transcription factors controlling expression of inflammatory adipokines and anti-inflammatory adipokines will be studied. TOBI will particularly investigate lipid-derived adipokines that have been little studied to date. Key molecules of pathophysiological relevance will be validated for their potential as targets for drug development. The TOBI consortium will mount a comprehensive collaborative program for analysing the molecular mechanisms underlying regulation of adipokine production and their function in target tissues using genetic, molecular and biochemical approaches. The consortium combines all necessary expertise to investigate the basis of the obesity-associated inflammatory drift. A TOBI toolbox will be developed that strengthen collaboration and comparability of results. In addition the consortium includes relevant partners to exploit the results by translating them into new treatment strategies for obesity-associated adipokine-mediated disorders.
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