Proinflammatory cytokines and endothelial dysfunction in obese subjects: effect of weight reduction

ABSTRACT

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. The aim of present study was to determine whether circulating levels of inflammatory cytokines and intercellular adhesion molecule-1 [sICAM-1] are elevated in obese subjects and whether they could be reduced by a substantical decrease in body weight. Forty-two healthy obese subjects [22 females and 20 males, age range 25 to 40 years, body mass index 35.2 +/- 3.64 Kg/m2, waist to hip ratio 0.883+0.085, and 20 age and sex matched normal weight controls were studied. Compared with nonobese subjects, obese subjects had increased basal concentrations of tumor necrosis factor-alpha [TNF-alpha]. [P<0.001], interleukin-6 [IL-6], [P<0.001] and sICAM-1 [P<0.001]. Flow mediated dilatation [FMD] was impaired in obese subjects when compared to lean controls [7.52% +/- 3.05 Vs 10.28% +/- 1.64, P<0.001]. Concentrations of TNF-alpha and lL-6 were related [P<0.001] to visceral obesity, as well as to slCAM-1 levels and FMD. After one year of a multidisciplinary program of weight reduction [diet, exercise, behavioral counseling], all obese women lost at least 10% of their original weight. Compared with baseline, sustained weight loss was associated with reduction of cytokines [TNF-alpha, IL-6] [P<0.001] and sICAM-1 [P = 0.001] concentrations in addition to improvement of FMD [P<0.001]. In obese subjects, endothelial activation and dysfunction correlates with visceral body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction in obese subjects: