Burden of obesity has increased significantly in the United States over last few decades. Association of obesity with insulin resistance and related cardiometabolic problems is well established. Traditionally, adipose tissue in visceral fat depot has been considered a major culprit in development of insulin resistance. However, growing body of the literature has suggested that adipose tissue in subcutaneous fat depot, not only due to larger volume but also due to inherent functional characteristics, can have significant impact on development of insulin resistance. There are significant differences in functional characteristics of subcutaneous abdominal/truncal versus gluteofemoral depots. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger vicious cycle of inflammation in subcutaneous adipose tissue and subsequent ectopic fat deposition. It is important to shift focus from fat content to functional heterogeneity in adipose tissue depots to better understand the relative role of subcutaneous adipose tissue in metabolic complications of obesity. Therapeutic lifestyle change continues to be the most important intervention in clinical practice at any level of increased adiposity. Future pharmaceutical interventions aimed at improving adipose tissue function in various subcutaneous depots have potential to help maintain adequate insulin sensitivity and reduce risk for development of insulin resistance complications. Prevalence of obesity has been increasing in the US. In 1960s, prevalence of obesity was approximately 13% [1]. The most recent analyses of National Health and Nutrition Examination Survey (NHANES) reported that 33.8% of adults (age 20 years or more) and 16.8% of children and adolescents (age 2–19 years) are obese [2, 3]. Obesity is associated with increased morbidity and mortality and decreased life expectancy. Obesity is associated with increased risk for cardiovascular diseases. These include coronary heart disease, heart failure, and sudden death [4, 5]. In fact heart disease is the leading cause of death (1 in every 4 deaths) for both men and women in the USA [6]. In addition to cardiovascular diseases, obesity is associated with numerous other medical conditions including type 2 diabetes, dyslipidemia, hypertension, nonalcoholic fatty liver disease, cancers, and sleep apnea [4]. Insulin resistance is the key underlying pathophysiologic process for development of many of these comorbidities. Medical costs associated with obesity have increased and were estimated at 147 billion
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