Effects of diet and serotonergic agonist on hepatic apolipoprotein B-100 secretion and endothelial function in obese men

We studied the effects of a hypocaloric diet with or without a serotonergic agonist (dexfenfluramine, of) on the hepatic secretion of very-low-density -lipoprotein (VLDL) apoB and endothelial function of the forearm microcircu lation in 20 viscerally obese men. The kinetics of VLDL apoB were studied u sing an infusion of 1-(C-13)-leucine. Isotopic enrichment of apo B was meas ured using gas-chromatography mass spectrometry, and a multicompartmental m odel was used to estimate kinetic functions. Forearm vasodilatation was mea sured following an ischaemic stimulus using strain-gauge plethysmography, a nd visceral adipose tissue mass using magnetic resonance imaging. Compared with leaner subjects, the obese men had significantly higher hepatic apoB s ecretion (p<0.05) and lower forearm flow debt repayment (p<0.001). Both tre atments produced similar decreases (p<0.05) in body weight, waist circumfer ence, visceral adipose tissue and fasting plasma insulin. With diet alone, there was a significant decrease (p<0.05) in the plasma concentration and p ool size hepatic secretion rate of VLDL apoB, as well as a significant incr ease (p<0.05) in post-ischaemic flow debt repayment. With diet plus Df, the re were parallel responses in these variables, but only decreased forearm v ascular resistance (p<0.05) was statistically significant. Combining both d ata sets, there was a highly significant reduction in hepatic apoB secretio n rate (20.9 +/- 2.0 vs. 14.7 +/- 1.6 mg/kg fat-free mass/day, p=0.005), as well as an increase in both maximal forearm blood flow (16.8 +/- 7.5 vs. 2 2.2 +/- 8.5 ml/100 ml/min, p=0.006) and flow debt repayment (3.5 +/- 2.1 vs . 5.4 +/- 2.8 ml/100 ml, p = 0.01), and a decrease in vascular resistance ( 6.7 +/- 3.7 vs. 5.1 +/- 4.4 mmHg/ml/100 ml/min, p = 0.007). Obese men have increased hepatic secretion of apoB and endothelial dysfunction of the fore arm microcirculation, and decreasing their visceral adipose tissue mass by diet (with or without a serotonergic agonist) improves these abnormalities. This may provide a mechanistic basis for the reduction in cardiovascular r isk in obese patients who lose weight.