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.


METHODS
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.
Sekhar
Rajagopal V
RV
Translation Metabolism Unit, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX 77030-2600, USA.
Jahoor
Farook
F
Pownall
Henry J
HJ
Rehman
Khaleel
K
Gaubatz
John
J
Iyer
Dinakar
D
Balasubramanyam
Ashok
A
D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D019540:Area Under Curve; D002245:Carbon Dioxide / Q000032:analysis / Q000378:metabolism; D002247:Carbon Isotopes; D016022:Case-Control Studies; D002855:Chromatography, Thin Layer; D002914:Chylomicrons / Q000737:chemistry; D004041:Dietary Fats / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000378:metabolism*; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D010084:Oxidation-Reduction; D019518:Postprandial Period; D014280:Triglycerides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019562:Viral Load
D002247:Carbon Isotopes; D002914:Chylomicrons; D004041:Dietary Fats; D014280:Triglycerides; D002245:Carbon Dioxide; C005859:tripalmitin