The metabolic syndrome (MetS) confers an increased risk for both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT) in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin) and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin), as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD. 1. Introduction The metabolic syndrome (MetS) comprises a cluster of cardiometabolic risk markers with insulin resistance and adiposity as central features [1–4]. Five diagnostic criteria for MetS have been identified (central obesity, dyslipidemia (high triglycerides (TGs) and/or low high-density lipoprotein cholesterol (HDL-C)), hypertension, and impaired fasting glucose) by the Adult Treatment Panel III (ATPIII) criteria of the National Cholesterol and Education Program (NCEP), and the presence of three of these features is considered sufficient to diagnose the syndrome [2, 4, 5]. Using this definition, the National Health and Nutrition Examination Survey (NHANES) data show that currently ~35% of all US adults have MetS [6] and that >40% of adults over the age of 50 have the syndrome [7]. It is important to emphasize that the diagnosis of MetS has been harmonized using the NCEP ATPIII criteria with the exception of different cut-points for waist circumference for different races [8]. Furthermore, MetS confers an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) [7, 9–12], both of which are additional risk factors for increased
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