title: Enhanced apoB48 metabolism in lipoprotein lipase X447 homozygotes.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.c.nierman@amc.uva.nl
authors.forename: Melchior C
authors.initials: MC
authors.lastname: Nierman
authors.forename: Jaap
authors.initials: J
authors.lastname: Rip
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Naohiko
authors.initials: N
authors.lastname: Sakai
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Monique G M
authors.initials: MG
authors.lastname: de Sain-van der Velden
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Berthil H C M T
authors.initials: BH
authors.lastname: Prinsen
mesh_terms: D053283:Apolipoprotein B-48 / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D053283:Apolipoprotein B-48; D002914:Chylomicrons; D008071:Lipoprotein Lipase