Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to hyperlipidemia in glycogen storage disease type 1a.
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-(13)C]acetate to quantify cholesterogenesis and lipogenesis. In a subset of patients, [1-(13)C]valine was given to assess lipoprotein metabolism and [2-(13)C]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 micromol/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 micromol/kg/min in patients and 3.8 +/- 1.9 micromol/kg/min in controls. Hyperlipidemia in GSD-1a is associated with strongly increased lipid production and a slower relative conversion of VLDL to LDL.
Center for Liver, Digestive and Metabolic Diseases, University of Groningen, Groningen, 9700 RB, The Netherlands.
Robert H J
RH
Bandsma
Berthil H
BH
Prinsen
Monique de Sain
Mde S
van Der Velden
Jan-Peter
JP
Rake
Theo
T
Boer
G Peter A
GP
Smit
Dirk-Jan
DJ
Reijngoud
Folkert
F
Kuipers
D000085:Acetates / Q000008:administration & dosage; D000328:Adult; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005990:Glycerol / Q000008:administration & dosage; D005953:Glycogen Storage Disease Type I / Q000150:complications / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology* / Q000378:metabolism; D007263:Infusions, Parenteral; D007700:Kinetics; D050155:Lipogenesis; D053419:Lipoproteins, IDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D010316:Particle Size; D014633:Valine / Q000008:administration & dosage
D000085:Acetates; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D014633:Valine; D005990:Glycerol