Lipoprotein lipase: regulation and role in lipoprotein metabolism

Olivecrona, Thomas; Hultin, Magnus; Bergö, Martin O.; Olivecrona, Gunilla

doi:10.1079/pns19970072

Cited by 49 publications

(36 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this situation, hyperinsulinaemia could result in more effective processing of TAGrich lipoproteins, chylomicrons (CM) and VLDL, through greater activation of the insulin-dependent pathways such as lipoprotein lipase (LPL), enhanced re-esterification of released fatty acids in the adipocyte, inhibition of hepatic VLDL production and a greater postprandial suppression of lipolysis through inhibition of hormone-sensitive lipase (HSL) activity. [61][62][63] In the present study, the expected positive correlation between insulin and plasma TAG, which was observed in the Caucasian men (r ¼ 0.318, P ¼ 0.19), was not observed in the Sikh men (r ¼ 0.011, P ¼ 0.94). This lack of association in the Sikh group tends to support the above hypothesis.…”

Section: Discussionmentioning

confidence: 58%

Lack of association between central adiposity and lipaemia in UK Sikh men

et al. 2003

View full text Add to dashboard Cite

OBJECTIVE: To determine whether the positive statistical associations between measures of total and regional adiposity and measures of glucose, insulin and triacylglycerol (TAG) metabolism reported in Caucasian men, are also observed in UK Sikhs. DESIGN: A matched cross-sectional study in which each volunteer provided a blood sample after a 12-h overnight fast and had anthropometric measurements taken. SUBJECTS: A total of 55 healthy Caucasian and 55 healthy UK Sikh men were recruited. The Caucasian and Sikh men were matched for age (48.7710.9 and 48.3710.0 y, respectively) and body mass index (BMI) (26.172.8 and 26.373.2 kg/m 2 , respectively). MEASUREMENTS: Anthropometric measurements were performed to assess total and regional fat depots. The concentrations of plasma total cholesterol, high-density cholesterol (HDL-C), low-density cholesterol (LDL-C) and small dense LDL (LDL3), TAG, glucose, fasting insulin (ins) and nonesterified fatty acids (NEFA) were analysed in fasted plasma. Surrogate measures of insulin resistance (HOMA-IR) and insulin sensitivity (RQUICKI) were calculated from insulin and glucose (HOMA-IR) and insulin, glucose and NEFA (RQUICKI) measurements. RESULTS: The Sikh men had significantly higher body fat, with the sum of the four skinfold measurements (Ssk) (P ¼ 0.0001) and subscapular skinfold value (P ¼ 0.009) higher compared with the Caucasian men. The Sikh volunteers also had characteristics of the metabolic syndrome: lower HDL-C (P ¼ 0.07), higher TAG (P ¼ 0.004), higher % LDL3 (P ¼ 0.0001) and insulin resistance (P ¼ 0.05 ). Both ethnic groups demonstrated positive correlations between insulin and waist circumference (Caucasian: r ¼ 0.661, P ¼ 0.0001; Sikh: r ¼ 0.477, P ¼ 0.0001). The Caucasian men also demonstrated significant positive correlations between central adiposity (r ¼ 0.275, P ¼ 0.04), other measures of adiposity (BMI and suprailiac skinfold) and plasma TAG, whereas the Sikh men showed no correlation for central adiposity (r ¼ 0.019, ns) and TAG with a trend to a negative relationship between other measures (Ssk and suprailiac) which reached near significance for subscapular skinfold and TAG (r ¼ À0.246, P ¼ 0.007). The expected positive association between insulin and TAG was observed in the Caucasian men (r ¼ 0.318, P ¼ 0.04) but not in the Sikh men (r ¼ 0.011, ns). CONCLUSIONS: In the Caucasian men, the expected positive association between plasma TAG and centralized body fat was observed. However, a lack of association between centralized, or any other measure of adiposity, and plasma TAG was observed in the matched Sikh men, although both ethnic groups showed the positive association between centralized body fat and insulin resistance, which was less strong for Sikhs. These findings in the Sikh men were not consistent with the hypothesis that there is a clear causal relationship between body fat and its distribution, insulin resistance, and lipid abnormalities associated with the metabolic syndrome, in this ethnic group.

show abstract

Section: Discussionmentioning

confidence: 58%

Lack of association between central adiposity and lipaemia in UK Sikh men

et al. 2003

View full text Add to dashboard Cite

show abstract

“…The LPL gene promoter contains a number of sequence motifs that are putatively responsive to a variety of hormonal and transcription factors (50) including response elements for PPAR␣ (51), SREBP1c (52,53) and LXR␣ (39). Despite this, much of the regulation of the enzyme protein occurs at the post-translational level (55). Insulin and dexamethasone have both been shown in vitro to up-regulate LPL activity markedly in adipocytes independently and synergistically, not only through the induction of LPL gene expression but quantitatively more importantly through post-transcriptional and post-translational regulations (56,57).…”

Section: Discussionmentioning

confidence: 99%

Hypertriglyceridemia in Lecithin-cholesterol Acyltransferase-deficient Mice Is Associated with Hepatic Overproduction of Triglycerides, Increased Lipogenesis, and Improved Glucose Tolerance

Xie

Maguire

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Lecithin-cholesterol acyltransferase deficiency is frequently associated with hypertriglyceridemia (HTG) in animal models and humans. We investigated the mechanism of HTG in the ldlr؊/؊ ؋ lcat؊/؊ (double knockout (dko)) mice using the ldlr؊/؊ ؋ lcat؉/؉ (knock-out (ko)) littermates as control. Mean fasting triglyceride (TG) levels in the dko mice were elevated 1.75-fold compared with their controls (p < 0.002). Both the very low density lipoprotein and the low density lipoprotein/intermediate density lipoprotein fractions separated by fast protein liquid chromatography were TG-enriched in the dko mice. In vitro lipolysis assay revealed that the dko mouse very low density lipoprotein (d < 1.019 g/ml) fraction separated by ultracentrifugation was a more efficient substrate for lipolysis by exogenous bovine lipoprotein lipase. Post-heparin lipoprotein lipase activity was reduced by 61% in the dko mice. Hepatic TG production rate, determined after intravenous Triton WR1339 injection, was increased 8-fold in the dko mice. Hepatic mRNA levels of sterol regulatory element binding protein-1 (srebp-1) and its target genes acetyl-CoA carboxylase-1 (acc-1), fatty acid synthase (fas), and stearoyl-CoA desaturase-1 (scd-1) were significantly elevated in the dko mice compared with the ko control. The hepatic mRNA levels of LXR␣ (lxr␣) and its target genes including angiopoietin-like protein 3 (angptl-3) in the dko mice were unchanged. Fasting glucose and insulin levels were reduced by 31 and 42%, respectively in the dko mice, in conjunction with a 49% reduction in hepatic pepck-1 mRNA (p ‫؍‬ 0.014). Both the HTG and the improved fasting glucose phenotype seen in the dko mice are at least in part attributable to an up-regulation of the hepatic srebp-1c gene.

show abstract

“…The major lipoprotein classes in each fraction were as follows: d Ͻ 1.006 g/ml, pre-␤-migrating VLDL; d ϭ 1.006 -1.02 g/ml, IDL; d ϭ 1.02-1.04 g/ml, large LDL; d ϭ 1.04 -1.06 g/ml, ␤-migrating small LDL and ␣-migrating HDL 1 ; d ϭ 1.06 -1.08 and 1.08 -1.10 g/ml, HDL 1 and HDL 2 ; and d ϭ 1.10 -1.21 g/ml, HDL 3 . Quantitative analysis of TC and TG in each fraction consistently showed three prominent changes in the relative amounts of different lipoproteins.…”

Section: Effect Of Increased Lpl Expression On Plasma Lipid Levels-asmentioning

confidence: 99%

“…15 and 16), and the cDNA sequence of human LPL shows about 80% homology to that of rabbit LPL. 3 Successful generation of transgenic rabbit lines required extensive effort and was made more difficult by a high rate of variability in the number of fertilized zygotes recovered from each donor rabbit, the small number of pups, and the relatively high rate of neonatal mortality, including cannibalism, as shown in Table I. A transgenic line (L17) was established and used for the current study.…”

Section: Fig 1 Northern Blot Analysis Of Hlpl Tissue Distribution (mentioning

confidence: 99%

“…Through the hydrolysis of TG in these particles, LPL converts these lipoproteins to denser lipoproteins such as chylomicron remnants, intermediate density lipoprotein (IDL), and low density lipoproteins (LDL) (1)(2)(3). This process generates free fatty acids (FFA), which are taken up and used for metabolic energy or stored as TG after reesterification and also results in the generation of surface remnants, which give rise to high density lipoproteins (HDL).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of Lipoprotein Lipase in Transgenic Rabbits Inhibits Diet-induced Hypercholesterolemia and Atherosclerosis

Fan¹,

Unoki²,

Kojima³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of TG-rich lipoproteins. To elucidate the physiological roles of LPL in lipid and lipoprotein metabolism, we generated transgenic rabbits expressing human LPL. In postheparinized plasma of transgenic rabbits, the human LPL protein levels were about 650 ng/ml, and LPL enzymatic activity was found at levels up to 4-fold greater than that in nontransgenic littermates. Increased LPL activity in transgenic rabbits was associated with as much as an 80% decrease in plasma triglycerides and a 59% decrease in high density lipoprotein-cholesterol. Analysis of the lipoprotein density fractions revealed that increased expression of the LPL transgene resulted in a remarkable reduction in the level of very low density lipoproteins as well as in the level of intermediate density lipoproteins. In addition, LDL cholesterol levels in transgenic rabbits were significantly increased. When transgenic rabbits were fed a cholesterol-rich diet, the development of hypercholesterolemia and aortic atherosclerosis was dramatically suppressed in transgenic rabbits. These results demonstrate that systemically increased LPL activity functions in the metabolism of all classes of lipoproteins, thereby playing a crucial role in plasma triglyceride hydrolysis and lipoprotein conversion, and that overexpression of LPL protects against diet-induced hypercholesterolemia and atherosclerosis. Lipoprotein lipase (LPL)1 plays a crucial role in lipid metabolism and transport by catalyzing the hydrolysis of triglyceriderich (TG-rich) lipoproteins such as chylomicrons and very low density lipoproteins (VLDL). Through the hydrolysis of TG in these particles, LPL converts these lipoproteins to denser lipoproteins such as chylomicron remnants, intermediate density lipoprotein (IDL), and low density lipoproteins (LDL) (1-3). This process generates free fatty acids (FFA), which are taken up and used for metabolic energy or stored as TG after reesterification and also results in the generation of surface remnants, which give rise to high density lipoproteins (HDL). It has been suggested that LPL influences not only plasma TG levels but also plasma HDL levels (4).LPL is mainly produced by mesenchymal cells such as adipose and muscle cells and then transported to the luminal surface of the vascular endothelium, where it is bound to heparan sulfate proteoglycans (HSPG). Small amounts of LPL are also present in other types of tissues, including the adrenals, brain, lung, and spleen (5). Furthermore, LPL is also expressed by macrophages and smooth muscle cells in atherosclerotic lesions (6, 7), suggesting that LPL modulates vascular functions and may be involved in atherogenesis. Elucidation of the precise roles of LPL in atherosclerosis has been compounded by the fact that LPL has multiple functions in lipoprotein metabolism through its catalytic properties and acts as a ligand for the LDL receptor-related protein (8) or a bridge between lipoproteins and HSPG (9). In humans, it has been found that familial L...

show abstract

Lipoprotein lipase: regulation and role in lipoprotein metabolism

Cited by 49 publications

References 10 publications

Lack of association between central adiposity and lipaemia in UK Sikh men

Lack of association between central adiposity and lipaemia in UK Sikh men

Hypertriglyceridemia in Lecithin-cholesterol Acyltransferase-deficient Mice Is Associated with Hepatic Overproduction of Triglycerides, Increased Lipogenesis, and Improved Glucose Tolerance

Overexpression of Lipoprotein Lipase in Transgenic Rabbits Inhibits Diet-induced Hypercholesterolemia and Atherosclerosis

Contact Info

Product

Resources

About