The metabolic syndrome is a clustering of obesity, diabetes, hyperlipidemia, and hypertension that is occurring in increasing frequency across the global population. that is rampant in both industrialized and developing countries is usually associated with an increase in obesity. For example, in a study of 12363 US men and women using the National Cholesterol Education Program’s Adult Treatment Panel III guidelines, the MS was diagnosed in 22.8% and 22.6% of the men and women, respectively . This syndrome was present in 4.6%, 22.4%, and 59% of normal weight, overweight, and obese men, respectively, and a similar distribution was observed in women. Higher body mass index (BMI), current smoking, low household income, high carbohydrate intake, and physical inactivity were associated with increased odds. Table 1 Comparison of definitions of the SB-207499 metabolic syndrome. The MS can be present in different forms, according to the combination of the different components of the syndrome, and it is well established that it increases the risk for the development of cardiovascular disease, type II diabetes, and cancer [5C7]. It is not yet known how the MS is usually triggered or how the different components are causally linked, but insulin SB-207499 resistance is usually strongly suspected as a common pathophysiologic link [8, 9], since it is usually clear that there is a positive correlation between body weight and insulin resistance and the risk of developing all the metabolic abnormalities associated with insulin resistance . However, recent data suggests that MS and obesity do SB-207499 not usually occur in concordance as there is some evidence for conditions of benign obesity [10C14]. For example, some studies suggest that frank obesity does not necessarily translate into insulin resistance and increased risk for AFX1 metabolic comorbidities. In a cross sectional study of 5440 participants of the National Health and Nutrition Examination Surveys 1999C2004, 31.7% of obese adults (BMI??30) were metabolically healthy . In general, healthy obesity describes the lack of any metabolic disorder including type II diabetes, dyslipidemia, and hypertension in an obese individual. To date, there is no prospective study of the healthy obese phenotype and there SB-207499 are a myriad of questions that can be resolved by studying this subtype of obesity. Amongst these are the following questions: do healthy obese subjects represent a delayed onset of obesity related insulin resistance, or is it a permanent condition? What are the causal factor(s) that lead the transition between healthy and unhealthy obese phenotypes? What is known with some clarity is usually that android excess fat distribution, visceral and ectopic excess fat accumulation, and insulin resistance are critical factors and potential causative parameters for the development of unhealthy obesity [15C17]. The association between the MS and inflammation is usually well documented . In an attempt to clarify the relationship between adiposity and SB-207499 inflammation, Welsh et al.  used a bidirectional Mendelian randomization approach and deduced that adiposity leads to higher C-reactive protein (CRP) levels, with no evidence for any reversal of this pathway. Accumulating evidence demonstrates a close link among the metabolic syndrome, a state of chronic inflammation, and oxidative stress . In fact, the oxidative stress-inflammation pathway has important roles in all the individual components of MS including vascular alterations [20C24]. 2. Oxidative Stress and Ectopic Excess fat Ectopic excess fat refers to the accumulation of triglycerides within cells of nonadipose tissue; these tissues normally contain only small amounts of excess fat. Visceral areas, liver, heart, and/or muscle are common sites for deposition of ectopic excess fat . The amount of ectopic excess fat is usually directly related to insulin.