This study was undertaken to evaluate the impact of fat gain and its distribution on endothelial function in lean healthy humans. For that purpose, 43 healthy volunteers with baseline body mass index (BMI) values between 18.5 and 24.9 kg/m2 were recruited (mean age=29 years; 18 women). Subjects were randomly assigned to gain weight (≈4 kg; n=35) or to maintain weight (n=8). Endothelial function was measured by brachial artery flow-mediated dilation, body composition was measured by dual-energy X-ray absorptiometry and abdominal fat areas by computed tomography. Results revealed that modest weight gain under standardized conditions of diet and activity was associated with attenuated endothelial function, even in the absence of changes in blood pressure. Moreover, endothelial function recovered after weight loss. An important finding was that endothelial dysfunction was significantly linked to intra-abdominal (visceral) but not to subcutaneous fat gain. On the other hand, endothelial function was not associated with changes in leptin, adiponectin, and C-reactive protein. These findings suggest that the development of endothelial dysfunction precedes any blood pressure increase and that it could be responsible for the link between abdominal obesity and cardiovascular risk.
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