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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #161947
Title: LIPOPROTEIN METABOLISM IN SUBJECTS WITH HEPATIC LIPASE DEFICIENCY

Author
item TILLY-KIESI, MARJU - HELSINKI HOSPITAL
item SCHAEFER, ERNST - TUFTS-HNRCA
item KNUDSEN, PETTERI - HELSINKI HOSPITAL
item WELTY, FRANCINE - TUFTS-HNRCA
item DOLNIKOWSKI, GREGORY - TUFTS-HNRCA
item TASKINEN, MARJA-RITTA - UNIVERSITY OF HELSINKI
item LICHTENSTEIN, ALICE - TUFTS-HNRCA

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2003
Publication Date: 4/1/2004
Citation: TILLY-KIESI, M., SCHAFER, E.J., KNUDSEN, P., WELTY, F., DOLNIKOWSKI, G., TASKINEN, M., LICHTENSTEIN, A.H. LIPOPROTEIN METABOLISM IN SUBJECTS WITH HEPATIC LIPASE DEFICIENCY. METABOLISM. 2004;53:520-5.

Interpretive Summary: The effect of a genetic alternation in a enzyme involved in the metabolism (processing) of lipoprotein particles in plasma was assessed using a non-radioactive marker. The enzyme, hepatic lipase, is made by the liver, and as has the ability to hydrolyze (break apart) two components of lipoprotein particles, triglyceride and phospholipid. Levels of lipoproteins have a strong impact on heart disease risk. Individuals with an abnormal hepatic lipase protein and control subjects were fed a standard diet and then administrated a non-radioactive tracer (leucine) in order to study the pattern of metabolism of their lipoprotein particles. Levels of triglyceride and HDL (good) cholesterol were higher and LDL (bad) cholesterol lower in the subjects with the abnormal hepatic lipase compared to control subjects. The higher triglyceride levels were accounted for by a lower fractional catabolic rate (degradation) and higher production rate of the main lipoprotein the carried triglyceride in the blood stream, very low density lipoprotein. This block in very low density lipoprotein metabolism accounted for the lower levels of low density lipoprotein particles. The higher levels of high density lipoprotein cholesterol were accounted for by a higher production rate in subjects with the abnormal hepatic lipase compared to control subjects. These data suggest that on a standard diet subjects with an abnormality in hepatic lipase have a lipoprotein profile that is associated with decreased risk of developing heart disease.

Technical Abstract: A heritable deficiency of hepatic lipase (HL) provides insights into the physiologic function of HL in vivo. The metabolism of apoB-100 in VLDL, IDL and LDL, and of apoA-I and apoA-II in HDL particles Lp(AI) and Lp(AI:AII) was assessed in two heterozygous males for compound mutations L334F/T383M or L334F/R186H, with 18% and 22% of HL activity, respectively, compared to six control males. Subjects were provided with a standard Western diet for a minimum of three weeks. At the end of the diet period apolipoprotein kinetics were assessed using a primed-constant infusion of [5,5,5-**2H3] leucine. Mean plasma 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.