Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity.

Endothelial cell dysfunction in obesity can be reduced by calorie restriction (CR), however it is unclear whether this benefit requires a concomitant weight loss or is it simply related to the reduced calorie intake per se. In our study serum was drawn from 41 obese women who were undergoing an 8-week dietary intervention with 15 - 30% energy deficit, and from 48 age- and sex-matched controls of normal weight. Serum was analysed for biomarkers of endothelial cell function, oxidative stress and inflammation. Compared with non-obese individuals, the obese patients had lower serum levels of nitric oxide (NO), adiponectin, and decreased serum antioxidant status. They also had significantly higher levels of adhesive molecules, thrombomodulin (TM), von Wilebrand factor (vWF), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin. To further characterize the effect of moderate CR, the patients were ranked into two comparable groups according to the extent of weight loss - below and above the median (-5.8 kg). A moderate dietary intervention did not correct adiponectin, antioxidant status, vWF, TM, and plasminogen activator inhibitor-1 (PAI-1) but ameliorated changes in other parameters. Only changes in NO and - to a lesser degree - in sE-selectin showed a clear relationship with the magnitude of weight reduction. By contrast, a beneficial reduction in TNF-α occurred equally in patients who lost more or less weight after caloric restriction. We concluded that moderate calorie restriction could still improve several parameters of endothelial cell function irrespective of whether it was accompanied by changes in body mass. However, a significant improvement in nitric oxide, a key mediator of endothelial well-being, requires a substantial reduction in body weight.