Context: Adipose tissue is increasingly recognized as an active endocrine organ with many secretory products and part of the innate immune system. With obesity, macrophages infiltrate adipose tissue, and numerous adipocytokines are released by both macrophages and adipocytes. Adipocytokines play important roles in the pathogenesis of insulin resistance and associated metabolic complications such as dyslipidemia, hypertension, and premature heart disease.
Evidence Acquisition: Published literature was analyzed with the intent of addressing the role of the major adipose secretory proteins in human obesity, insulin resistance, and type 2 diabetes.
Evidence Synthesis: This review analyzes the characteristics of different adipocytokines, including leptin, adiponectin, pro-inflammatory cytokines, resistin, retinol binding protein 4, visfatin, and others, and their roles in the pathogenesis of insulin resistance.
Conclusions:
Inflamed fat in obesity secretes an array of proteins implicated in the impairment of insulin signaling. Further studies are needed to understand the triggers that initiate inflammation in adipose tissue and the role of each adipokine in the pathogenesis of insulin resistance. (J Clin Endocrinol Metab 93: S64 -S73, 2008) M any recent epidemiological studies have documented the rapid increase in the prevalence of obesity. According to data from the Center for Disease Control Behavioral Risk Factor Surveillance System, 22 states in the United States have an obesity [body mass index (BMI) ΟΎ30 kg/m 2 ] prevalence of over 30% in 2006, whereas only 10 yr earlier, no state had an obesity prevalence of more than 20%. Along with the increase in obesity is a parallel increase in the prevalence of type 2 diabetes, impaired glucose tolerance (1, 2), and other complications of obesity, such as hypertension, sleep apnea, and arthritis. Whether or not the obesity epidemic leads to an increase in the incidence of new obesity related malignancies remains to be determined (3,4). A recent study suggested that future life expectancy may decrease for the first time due to the increase in obesity (5).
The metabolic complications of obesity, often referred to as the metabolic syndrome, consist of insulin resistance, often culminating in β€-cell failure, impaired glucose tolerance and type 2 diabetes, dyslipidemia, hypertension, and premature heart disease. Abdominal obesity, ectopic lipid accumulation, hepatic ste-atosis, and sleep apnea can also be included in the metabolic complications of obesity (6).
This paper is intended to provide an overview of the pathogenesis of the metabolic complications of obesity, with particular emphasis on the role of inflammation and adipose tissue-derived proteins. There are many adipokines, and space limitations do not permit a thorough discussion of all of them. Therefore, this review will discuss a number of the major adipokines, and will focus on adipokines related to inflammation, and in particular adipokines that have been the subject of studies in humans, and where there are clinical implications for obesity and insulin resistance.
Obesity Is Associated with Inflammation
The role of adipose tissue in metabolic syndrome has continued to evolve with the description of numerous secretory products from adipocytes. These "adipokines" are important determi-