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

Watts, G.F., Herrmann, S. and Riches, F.M. (2000) Effects of diet and serotonergic agonist on hepatic apolipoprotein B-100 secretion and endothelial function in obese men. QJM, 93 (3). pp. 153-161.

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We studied the effects of a hypocaloric diet with or without a serotonergic agonist (dexfenfluramine, Df) on the hepatic secretion of very‐low‐density‐lipoprotein (VLDL) apoB and endothelial function of the forearm microcirculation in 20 viscerally obese men. The kinetics of VLDL apoB were studied using an infusion of 1‐(13C)‐leucine. Isotopic enrichment of apo B was measured using gas‐chromatography mass spectrometry, and a multicompartmental model was used to estimate kinetic functions. Forearm vasodilatation was measured following an ischaemic stimulus using strain‐gauge plethysmography, and visceral adipose tissue mass using magnetic resonance imaging. Compared with leaner subjects, the obese men had significantly higher hepatic apoB secretion (p<0.05) and lower forearm flow debt repayment (p<0.001). Both treatments produced similar decreases (p<0.05) in body weight, waist circumference, visceral adipose tissue and fasting plasma insulin. With diet alone, there was a significant decrease (p<0.05) in the plasma concentration and pool size hepatic secretion rate of VLDL apoB, as well as a significant increase (p<0.05) in post‐ischaemic flow debt repayment. With diet plus Df, there were parallel responses in these variables, but only decreased forearm vascular resistance (p<0.05) was statistically significant. Combining both data sets, there was a highly significant reduction in hepatic apoB secretion 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. 22.2±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 forearm 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 risk in obese patients who lose weight.

Item Type: Journal Article
Publisher: Oxford University Press
Copyright: © Association of Physicians
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