Primary Lipoprotein Lipase Deficiency

Brunzell, John D.; Iverius, Per-Henrik; Scheibel, M.; Hayden, Michael R.; McLeod, Roger S.; Frolich, Jiri

doi:10.1007/978-1-4684-1262-8_20

Cited by 37 publications

(39 citation statements)

References 33 publications

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“…Two half-sisters, IG and JG, were also studied and had approximately half the normal levels of HL activity. The HL-deficient subject (PG) had been taking ctofibrate since 1966 (which resulted in a drop of his TG from the 2000 to 4000 mg/dl range to less than 1000 mg/dl), 16 while IG and JG were not on lipid-lowering drugs or other medications that affect lipid metabolism.…”

Section: Study Subjectsmentioning

confidence: 99%

Large buoyant LDL-like particles in hepatic lipase deficiency.

et al. 1989

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Hepatic lipase (HL) Is thought to play a role In processing very low density llpoproteln to low density llpoproteln (LDL). To analyze the relationship between HL and LDL, the density, size, and chemical composition of LDL Isolated from 18 normal subjects and from three subjects with reduced or absent levels of HL activity were compared. In an HL-deficlent subject the major peak of apoproteln (apo) Bcontalning llpoprotelns ('LDL') had a density of 1.023 g/ml and a diameter of 26.4 nm compared to male control subjects (1.044±0.006 g/ml and 25.3±0.3 nm). Two half-sisters of the HL-deflclent subject with half the normal levels of HL activity had LDL that also were more buoyant and slightly larger than the LDL Isolated from female control subjects. The peak density and average diameter of LDL were correlated with HL activity, consistent with the hypothesis that HL Influenced formation and physical characteristics of typical LDL. Apo B-100 was the major apoproteln In the 'LDL' isolated from the HL-deflclent subject and contained a greater proportion of trlglycerlde compared to the control subjects' LDL. The absence of HL appears to prevent the production of classical LDL Our data support the hypothesis that HL helps determine normal LDL characteristics. . A complicated picture of a 'delipidation cascade' is emerging in which the factors that determine whether VLDL will be removed from the circulation or undergo conversion into LDL is just being delineated. Several intravascular enzymes are thought to be involved in the formation of LDL, including lipoprotein lipase (LPL), llpid transfer protein, and hepatic triglyceride lipase (HL). Rubinstein et al. 3 have hypothesized that HL is involved in the conversion of IDL to LDL; however, direct experimental data describing the mechanisms involved in this conversion are, as yet, undefined. 34The conversion of VLDL remnants or IDL to LDL is thought to occur across the splanchnic bed where HL is located.35 Support for a role of HL among the factors involved in the processing of IDL to LDL has been derived from observations made on humans and animals with HL deficiency; humans wtth diseases associated with reduced levels of HL activity (hypothyroidism, uremia, chronic liver disease); and in experimentally induced HL deficiency in rats and monkeys. 11 -15 In these studies, reduced levels of HL were associated with an increase in IDL concentration and TG accumulation in LDL.6 - 14The present study was designed to examine the possible relationships between HL activity and LDL physical characteristics in normolipidemic subjects and in subjects with reduced or absent HL activity levels. Methods Study SubjectsEighteen healthy Caucasian subjects (nine women and nine men), with a mean age of 35.4±11.3 years for women and 26.9±5.6 years for men (range, 18 to 48 years), were recruited for this study, and they participated on a voluntary basis. None of these subjects took any medication or had evidence of a lipoprotein disorder. All patients belonged to a single family with HL defic...

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Section: Study Subjectsmentioning

confidence: 99%

Large buoyant LDL-like particles in hepatic lipase deficiency.

et al. 1989

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“…One significant limitation in designing efficacy trials in familial LPLD is the limited number of patients available for participation. Familial LPLD is characterized as an ultra-orphan disease with a prevalence of only 1 per million (Brunzell, 1999). The investigators further limited participation in the trial in several ways including the requirement that subjects have substantial levels of circulating endogenous (but defective) LPL enzyme as a way to avoid transgene-specific B and T cell responses.…”

Section: Discussionmentioning

confidence: 99%

“…Familial lipoprotein lipase deficiency (LPLD) is a rare, autosomal recessive disorder affecting about 1 person per million (Brunzell, 1999). The underlying pathophysiology of LPLD is a lack of functionally active lipoprotein lipase (LPL), which plays an important role in triglyceride (TG), chylomicron (CM), and very low-density lipoprotein (VLDL) metabolism ( Fig.…”

Section: The Diseasementioning

confidence: 99%

Lessons Learned from the Clinical Development and Market Authorization of Glybera

Bryant

Christopher²,

Giles³

et al. 2013

Human Gene Therapy Clinical Development

169

133

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“…It is one of several tissues that expresses LPL (EC 3.1.1.34), an enzyme that is involved in the clearance of circulating triglycerides by catalyzing the hydrolysis of the triglyceride core of circulating lipoproteins. Generalized transgenic (Tg) overexpression of LPL in mice results in a reduction of serum triglycerides and an increase in HDL cholesterol (9), whereas extreme hypertriglyceridemia has been observed in humans (10), cats (11,12), and mice (13) lacking LPL. The discordant regulation of LPL in skeletal muscle and adipose tissue serves to traffic circulating lipids toward oxidation or storage, depending upon the metabolic context (14).…”

mentioning

confidence: 99%

Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype?

Jensen

Knaub

Konhilas

et al. 2008

Journal of Lipid Research

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LPL is an enzyme involved in the breakdown and uptake of lipoprotein triglycerides. In the present study, we examined how the transgenic (Tg) overexpression of human LPL in mouse skeletal muscle affected tolerance to cold temperatures, cold-induced thermogenesis, and fuel utilization during this response. Tg mice and their nontransgenic controls were placed in an environmental chamber and housed in metabolic chambers that monitored oxygen consumption and carbon dioxide production with calorimetry. When exposed to 4jC, an attenuation in the decline in body temperature in Tg mice was accompanied by an increased metabolic rate (15%; P , 0.001) and a reduction in respiratory quotient (P , 0.05). Activity levels, the expression of uncoupling proteins in brown fat and muscle, and lean mass failed to explain the enhanced cold tolerance and thermogenesis in Tg mice. The more oxidative type IIa fibers were favored over the more glycolytic type IIb fibers (P , 0.001) in the gastrocnemius and quadriceps muscles of Tg mice. These data suggest that Tg overexpression of LPL in skeletal muscle increases cold tolerance by enhancing the capacity for fat oxidation, producing an avian-like phenotype in which skeletal muscle contributes significantly to the thermogenic response to cold temperatures.-Jensen, D. R., L. A. Knaub, J. P. Konhilas, L. A. Leinwand, P. S. MacLean, and R. H. Eckel. Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype? J. Lipid Res. 2008. 49: 870-879.

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Primary Lipoprotein Lipase Deficiency

Cited by 37 publications

References 33 publications

Large buoyant LDL-like particles in hepatic lipase deficiency.

Large buoyant LDL-like particles in hepatic lipase deficiency.

Lessons Learned from the Clinical Development and Market Authorization of Glybera

Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype?

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