Enhanced apoB48 metabolism in lipoprotein lipase X447 homozygotes

Melchior C Nierman, Jaap Rip, Jan Albert Kuivenhoven, Naohiko Sakai, John J P Kastelein, Monique G M de Sain-van der Velden, Erik S G Stroes, Berthil H C M T Prinsen

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Abstract

RATIONALE: Lipoprotein lipase (LPL) X447 homozygotes are characterized by enhanced conversion of TRL apoB100. Here, we set out to investigate whether this LPL variant is also associated with enhanced apoB48 clearance. Therefore, we evaluated apoB48 kinetics in X447 homozygotes in the fed state by infusion of isotope L-[1-(13)C]-valine and subsequent compartmental modeling.

METHODS AND RESULTS: ApoB48 metabolism was assessed in five X447 homozygotes (X/X genotype) and five S447 homozygotes (S/S genotype). Subjects were continuously fed and received infusion of stable isotope L-[1-(13)C]-valine. Results were analyzed by SAAM II modeling. Fasting (2.4-fold, p=0.02) as well as non-fasting (1.6-fold, p=0.09) apoB48 concentration was increased in the X447 homozygotes compared to S447 homozygotes. In addition, the X447 homozygotes exhibited a 1.7-fold higher apoB48 poolsize (p=0.04). Interestingly, apoB48 fractional catabolic rate (FCR) was 1.9-fold higher (p=0.007) and apoB48 synthesis was more than two-fold higher (p=0.006) in the X447 homozygotes compared to S447 homozygotes.

CONCLUSION: In the present study, we show that X447 homozygotes exhibit enhanced apoB48 clearance. Previously, these homozygotes were shown to present with enhanced apoB100 TRL conversion. Combined, this LPLS447X gain of function variant affects apoB48 as well as apoB100 TRL metabolism.

Original languageEnglish
Pages (from-to)446-451
Number of pages6
JournalATHEROSCLEROSIS
Volume194
Issue number2
DOIs
Publication statusPublished - Oct-2007

Keywords

  • lipoprotein lipase
  • X447
  • apoB48
  • chylomicron
  • metabolism
  • TRIGLYCERIDE-RICH LIPOPROTEINS
  • STABLE-ISOTOPES
  • APO-B-100 KINETICS
  • B-100 KINETICS
  • GENE VARIATION
  • HEART-DISEASE
  • B-48
  • CARRIERS
  • HUMANS
  • APOLIPOPROTEIN-B-48

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