Severely dysregulated disposal of postprandial triacylglycerols exacerbates hypertriacylglycerolemia in HIV lipodystrophy syndrome.

BACKGROUND The pathogenesis of hypertriacylglycerolemia, a characteristic feature of HIV lipodystrophy syndrome (HLS), is incompletely understood. One mechanism is accelerated lipolysis in the fasted state, but the severity of the hypertriacylglycerolemia suggests that additional underlying abnormalities may exist in the disposal of dietary fat. OBJECTIVE Our objective was to investigate abnormalities in dietary fat disposal in the pathogenesis of hypertriacylglycerolemia in HLS. DESIGN We studied 6 nondiabetic men with HLS and 6 men without HIV matched for age and body mass index as control subjects for 8 h after consumption of an isocaloric meal containing 2 g labeled [(13)C(3)]tripalmitin. Chylomicron-triacylglycerol disposal was estimated from labeled [(13)C(1)]palmitate in the plasma chylomicron fraction, and [(13)C(1)]palmitate oxidation was estimated from the (13)CO(2) enrichment in the breath and CO(2) production, over 8 h after the meal. RESULTS HLS patients had significantly elevated concentrations of fasting plasma triacylglycerols in both chylomicron (x + SE: 100.3 +/- 49.5 compared with 29.2 +/- 2.2 mg/dL; P < 0.01) and VLDL (82.4 +/- 39.0 compared with 10.8 +/- 2.8 mg/dL; P < 0.01) fractions. Chylomicron-triacylglycerol-derived [(13)C(1)]palmitate disposal was markedly lower in the HLS patients (3.09 +/- 0.41 compared with 6.42 +/- 0.18 mmol [(13)C(1)]palmitate/8 h; P < 0.001) in the 8-h postmeal period. Further, HLS patients had lowered storage of chylomicron-triacylglycerols (0.74 +/- 0.38 compared with 5.05 +/- 0.16 mmol; P < 0.0001) and elevated plasma [(13)C(1)]palmitate concentrations (2.01 +/- 0.27 compared with 1.18 +/- 0.16 mmol; P < 0.05) 8 h after the meal. CONCLUSIONS Patients with HLS have key defects that markedly impair postprandial disposal and storage of chylomicron-triacylglycerols. These defects contribute significantly to hypertriacylglycerolemia in HLS.