Metabolic syndrome is a disease characterized by increased waist circumference and at least two of the following criteria: increased fasting serum glucose, triglycerides, blood pressure and low HDL cholesterol concentration. This condition has been shown associated to increased cardiovascular risk and accelerated atherosclerosis. The pathophysiological mechanisms underlying metabolic syndrome are currently under investigation to identify molecular targets for better characterizing cardiovascular risk and more selective therapies. Although insulin resistance has been proposed as a main player in the pathophysiology of metabolic syndrome, recent evidence clearly showed that its importance for diagnosis has been dramatically reduced. In particular, it is not clear if insulin resistance is the cause or the result of metabolic syndrome. At present, other soluble mediators, such as inflammatory cytokines, adipokines, coagulatory factors, and alterations in free fatty acid metabolism, are considered crucial players in the development of metabolic syndrome. This special issue will be focused on new soluble mediators as promising candidates to better assess the cardiovascular risk in metabolic syndrome. In particular, the pathophysiological role of adipocytokines, cytokines, and chemokines will be discussed. The controversies on the role of insulin resistance will be discussed. Finally, the potential protective role of morbid obesity on the cardiovascular risk will be debated. An update on the therapeutic strategies to improve metabolic syndrome will be included in the issue. Potential topics include, but are not limited to:

• The pathophysiology of metabolic syndrome: update on inflammatory molecules and cell subsets
• Insulin resistance: controversies in metabolic syndrome
• The inflammatory role of insulin in metabolic syndrome pathophysiology
• The association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome
• Novel promising inflammatory biomarkers and factors in metabolic syndrome patients
• Obesity and inflammation: role for adipocytokines
• Obesity and morbid obesity: two entities of a paradox?
• Lipid disorders, inflammation, and insulin resistance
• Chemokines, cytokines, and their selective blockade to reduce metabolic syndrome-associated cardiovascular risk
• Update on guidelines to manage cardiovascular risk in metabolic syndrome
• Update on the treatments targeting metabolic syndrome cluster

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