Obesity Epidemiology

152 EPIDEMIOLOGIC STUDIES OF CONSEQUENCES OF OBESITYadipocyte-secreted cytokines may be the underlying pathophysiology in the developmentof insulin resistance and the metabolic syndrome. For this reason, the metabolic syndromehas also been called “the inflammatory syndrome.” 14Excess adiposity, especially abdominal obesity, is recognized as the primary drivingforce behind the current epidemic of the metabolic syndrome. Although mechanismslinking obesity to elevated risk of individual components of the syndrome are not yetfully understood, evidence suggests that specific hormones, cytokines, and free fattyacids (FFAs) secreted by adipose tissue play crucial roles. Demonstration of crosstalkbetween adipose tissue and other insulin target tissues (e.g., skeletal muscle and liver) hasgreatly advanced our understanding of the link between obesity and insulin resistance. 15,16Such crosstalk is mediated through molecules released by adipocytes, including leptin,tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), resistin, and adiponectin 17(Fig. 8.2). Acting in concert, these cytokines or adipokines play critical roles in energymetabolism and insulin sensitivity. 16 Epidemiologic studies have consistently demonstratedpositive associations between overall and central adiposity and increased plasmaconcentrations of leptin, TNF-α, and IL-6. Subjects with obesity, insulin resistance,and type 2 diabetes have lower plasma levels of adiponectin. 18 Resistin’s relationship toobesity and insulin resistance is not as clear. 19 Recent data suggest that retinol-bindingprotein 4 (RBP4), another protein secreted by adipocytes, is linked to insulin resistanceand type 2 diabetes. 20ObesityAdipocytesPAI-1 Leptin Adiponectin TNF-AngiotensinResistinNFBCardiovascular effects, sleep apneaRenal effectsActivation of the sympathetic nervous systemMetabolic effects (dyslipidemia, carbohydrate intolerance)Endocrine effects (hyperinsulinism, insulin resistance,hypercortisolism, increased erythropoietin secretion)Increased coagulation/decreased fibrinolysis ( PAI-1)Figure 8.2 Influence of adipose tissue hormones or proteins on obesity-associated organic andmetabolic abnormalities. Angiotensin and adiponectin are active both via the NFκB pathwayor directly by other pathways. ↑, increased in obesity; ↓, decreased in obesity; NFκB, nuclearfactor-kappa B. PAI-1 denotes plasminogen activator inhibitor-1. Adapted from Wiecek A,Kokot F, Chudek J, Adamczak M. The adipose tissue—a novel endocrine organ of interest to thenephrologist. Nephrol Dial Transplant. 2002;17:191-195. 17