ADAPT · Adipokines as Drug Targets to Combat Adverse Effects of Excess Adipose Tissue

Obesity represents the major risk factor for the cardiometabolic syndrome, which is an epidemic disease that generates a severe global socio-economic burden for the public health systems. Enhanced production of proinflammatory adipocytokines by expanded adipose tissue is now considered as a key event in the pathogenesis of this syndrome. This process involves i) the systemic release of adipokines, preferentially by visceral abdominal fat and ii) the paracrine, adipokine-mediated crosstalk between periorganic fat and different organs including skeletal and cardiac muscle. Members of the ADAPT consortium have pioneered this novel view of adipose tissue as an active endocrine organ. However, there is very limited knowledge if adipokines and their downstream signalling pathways may represent “drugable” targets potentially opening new avenues to combat the devastating complications linked to obesity and the cardiometabolic syndrome. Therefore, the major goal of this project is to identify novel or existing adipocytokines as drug targets that could be used to reverse obesity-associated inflammation and adverse reactions related to excess fat, as outlined in the work programme. For this purpose the mustidisciplinary ADAPT consortium has been formed which integrates basic and clinical science, bioinformatics, in silico drug design and the specific expertise of a large pharmaceutical company. To reach the objectives, a stepwise strategy will be used including i) the identification of novel adipocytokines and the cellular sources and regulation of adipokine production, ii) the analysis of intraorgan crosstalk within adipose tissue which plays a pivotal role in adipose tissue inflammation, iii) the assessment of interorgan crosstalk with a focus on skeletal and cardiac muscle and the role of brown fat and iv) the pharmacological and clinical evaluation of adipokines as drug targets and potential biomarkers.