Q J Med 2000; 93: 153-161
© 2000 Association of Physicians
Effects of diet and serotonergic agonist on hepatic apolipoprotein B-100 secretion and endothelial function in obese men
From the University Department of Medicine and Western Australian Heart Research Institute, University of Western Australia, Royal Perth Hospital, Perth, Australia
Received 4 August 1999 and in revised form 11 January 2000
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.
Address correspondence to Associate Professor G.F. Watts, University Department of Medicine, Royal Perth Hospital, Box X2213 GPO Perth 6001, Western Australia, Australia. e\|[hyphen]\|mail: gfwatts{at}cyllene.uwa.edu.au
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