Abstract
Glycogen storage disease type 1a (GSD-1a) is a metabolic disorder characterized by fasting-induced hypoglycemia, hepatic steatosis, and hyperlipidemia. The mechanisms underlying the lipid abnormalities are largely unknown. To investigate these mechanisms seven GSD-1a patients and four healthy control subjects received an infusion of [1-13C]acetate to quantify cholesterogenesis and lipogenesis. In a subset of patients, [1-13C]valine was given to assess lipoprotein metabolism and [2-13C]glycerol to determine whole body lipolysis. Cholesterogenesis was 274 ± 112 mg/d in controls and 641 ± 201 mg/d in GSD-1a patients (p < 0.01). Plasma triglyceride-palmitate derived from de novo lipogenesis was 7.1 ± 9.4 and 86.3 ± 42.5 μmol/h in controls and patients, respectively (p < 0.01). Production of VLDL did not show a consistent difference between the groups, but conversion of VLDL into intermediate density lipoproteins was relatively retarded in all patients (0.6 ± 0.5 pools/d) compared with controls (4.3 ± 1.8 pools/d). Fractional catabolic rate of intermediate density lipoproteins was lower in patients (0.8 ± 0.6 pools/d) compared with controls (3.1 ± 1.5 pools/d). Whole body lipolysis was similar, i.e., 4.5 ± 1.9 μmol/kg/min in patients and 3.8 ± 1.9 μmol/kg/min in controls. Hyperlipidemia in GSD-1a is associated with strongly increased lipid production and a slower relative conversion of VLDL to LDL.
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Abbreviations
- CHREBP:
-
carbohydrate-response element binding protein
- G6Pase-α:
-
glucose-6-phosphatase α
- GSD:
-
glycogen storage disease
- IDL:
-
intermediate density lipoprotein
- LXR:
-
liver-X receptor
- SREBP:
-
sterol regulatory element-binding protein
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Acknowledgements
We thank Anke ter Harmsel and Theo van Dijk for excellent technical support.
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This work was supported by a grant from the Dutch Foundation for Scientific Research (NWO 920-03-123) and a grant from the Netherlands Diabetes Research Foundation (DFN 96.604).
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Bandsma, R., Prinsen, B., de Sain-van der Velden, M. et al. Increased de novo Lipogenesis and Delayed Conversion of Large VLDL into Intermediate Density Lipoprotein Particles Contribute to Hyperlipidemia in Glycogen Storage Disease Type 1a. Pediatr Res 63, 702–707 (2008). https://doi.org/10.1203/PDR.0b013e31816c9013
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DOI: https://doi.org/10.1203/PDR.0b013e31816c9013
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