title: Lipoprotein metabolism in subjects with hepatic lipase deficiency.
abstract: A heritable deficiency of hepatic lipase (HL) provides insights into the physiologic function of HL in vivo. The metabolism of apolipoprotein B (apoB)-100 in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) and of apoA-I and apoA-II in high-density lipoprotein (HDL) particles lipoprotein (Lp)(AI) and Lp(AI:AII) was assessed in 2 heterozygous males for compound mutations L334F/T383M or L334F/R186H, with 18% and 22% of HL activity, respectively, compared with 6 control males. Subjects were provided with a standard Western diet for a minimum of 3 weeks. At the end of the diet period, apo kinetics was assessed using a primed-constant infusion of [5,5,5-(2)H(3)] leucine. Mean plasma triglyceride (TG) and HDL cholesterol levels were 55% and 12% higher and LDL cholesterol levels 19% lower in the HL patients than control subjects. A higher proportion of apoB-100 was in the VLDL than IDL and LDL fractions of HL patients than control subjects due to a lower VLDL apoB-100 fractional catabolic rate (FCR) (4.63 v 9.38 pools/d, respectively) and higher hepatic production rate (PR) (33.24 v 10.87 mg/kg/d). Delayed FCR of IDL (2.78 and 6.31 pools/d) and LDL (0.128 and 0.205 pools/d) and lower PR of IDL (3.67 and 6.68 mg/kd/d) and LDL 4.57 and 13.07 mg/kg/d) was observed in HL patients relative to control subjects, respectively. ApoA-I FCR (0.09 and 0.13 pools/d) and PR (4.01 and 6.50 mg/kg/d) were slower in Lp(AI:AII) particles of HL patients relative to control subjects, respectively, accounting for the somewhat higher HDL cholesterol levels. HL deficiency may result in a lipoprotein pattern associated with low heart disease risk.
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Marju
authors.initials: M
authors.lastname: Tilly-Kiesi
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Petteri
authors.initials: P
authors.lastname: Knudsen
authors.forename: Francine K
authors.initials: FK
authors.lastname: Welty
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Dolnikowski
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood / Q000493:pharmacokinetics; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D006579:Heterozygote; D006801:Humans; D008049:Lipase / Q000172:deficiency*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010316:Particle Size; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D008049:Lipase