Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/25/2005
Publication Date: 6/1/2005
Citation: Sekhar, R.V., Jahoor, F., Pownall, H.J., Rehman, K., Gaubatz, J., Iyer, D., Balasubramanyam, A. 2005. Severely dysregulated disposal of postprandial triacylglycerols exacerbates hypertriacylgycerolemia in HIV lipodystrophy syndrome. American Journal of Clinical Nutrition. 81:1405-1410. Interpretive Summary: Patients infected with HIV are now developing a new condition called HIV lipodystrophy syndrome. This condition is characterized by high blood cholesterol and triglyceride concentrations which are known to cause cardiovascular disease with time. High blood cholesterol and triglyceride concentrations are usually caused by alterations in fat metabolism. The goal of this study was to determine what changes in dietary fat metabolism was causing blood triglycerides to rise in individuals with HIV. We hypothesized that the individuals with HIV lipodystrophy syndrome were unable to remove and store triglycerides entering their blood from a meal. Studies were performed in 6 HIV-infected men with HIV lipodystrophy and 6 uninfected healthy men. The men were all fed a meal that contained triglycerides labeled with a stable isotope of carbon so the fate of the triglyceride can be traced in the blood. We found that the patients with HIV lipodystrophy syndrome were removing triglycerides from their circulation more slowly than the healthy men. They were also storing the triglycerides at a much slower rate. This finding suggested that defective removal from the blood and storage of triglycerides was the cause of high blood triglycerides in patients with HIV lipodystrophy syndrome.
Technical Abstract: 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. Our objective was to investigate abnormalities in dietary fat disposal in the pathogenesis of hypertriacylglycerolemia in HLS. 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. 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. Patients with HLS have key defects that markedly impair postprandial disposal and storage of chylomicron-triacylglycerols. These defects contribute significantly to hypertriacylglycerolemia in HLS.