Hepatic and extrahepatic uptake of intravenously injected lipoprotein lipase

Wallinder, Lars; Peterson, Jonas; Olivecrona, Thomas; Bengtsson‐Olivecrona, Gunilla

doi:10.1016/0005-2760(84)90181-4

Cited by 112 publications

(64 citation statements)

References 20 publications

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“…It seems possible that GPIHBP1 in the liver also functions to bind enzymatically active LPL homodimers and remove them from the bloodstream. Indeed, there is some evidence that the liver carries out this function (22,23).…”

Section: Discussionmentioning

confidence: 99%

Unexpected Expression Pattern for Glycosylphosphatidylinositol-anchored HDL-binding Protein 1 (GPIHBP1) in Mouse Tissues Revealed by Positron Emission Tomography Scanning

Olafsen

Young

Davies

et al. 2010

Journal of Biological Chemistry

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Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), a GPI-anchored endothelial cell protein, binds lipoprotein lipase (LPL) and transports it into the lumen of capillaries where it hydrolyzes triglycerides in lipoproteins. GPIHBP1 is assumed to be expressed mainly within the heart, skeletal muscle, and adipose tissue, the sites where most lipolysis occurs, but the tissue pattern of GPIHBP1 expression has never been evaluated systematically. Because GPIHBP1 is found on the luminal face of capillaries, we predicted that it would be possible to define GPIHBP1 expression patterns with radiolabeled GPIHBP1-specific antibodies and positron emission tomography (PET) scanning. In Gpihbp1 ؊/؊ mice, GPIHBP1-specific antibodies were cleared slowly from the blood, and PET imaging showed retention of the antibodies in the blood pools (heart and great vessels). In Gpihbp1 ؉/؉ mice, the antibodies were cleared extremely rapidly from the blood and, to our surprise, were taken up mainly by lung and liver. Immunofluorescence microscopy confirmed the presence of GPIHBP1 in the capillary endothelium of both lung and liver. In most tissues with high levels of Gpihbp1 expression, Lpl expression was also high, but the lung was an exception (very high Gpihbp1 expression and extremely low Lpl expression). Despite low Lpl transcript levels, however, LPL protein was readily detectable in the lung, suggesting that some of that LPL originates elsewhere and then is captured by GPIHBP1 in the lung. In support of this concept, lung LPL levels were significantly lower in Gpihbp1 ؊/؊ mice than in Gpihbp1 ؉/؉ mice. In addition, Lpl ؊/؊ mice expressing human LPL exclusively in muscle contained high levels of human LPL in the lung.The triglyceride-rich lipoproteins (chylomicrons and very low density lipoproteins) undergo lipolytic processing in the capillaries of peripheral tissues, mainly in heart and skeletal muscle, where the lipids are used as fuel, and in adipose tissue, where the lipids are stored (1). Lipolysis depends on lipoprotein lipase (LPL), 4 an enzyme that is synthesized and secreted at high levels by myocytes and adipocytes (1, 2). A deficiency of LPL results in extremely high levels of triglycerides in the blood, both in humans (2) and in animal models (3, 4).For many decades, the mechanism by which LPL reached the lumen of capillaries was mysterious, but this puzzle was solved recently. GPIHBP1 (glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1), a GPIanchored protein of capillary endothelial cells (5, 6), transports LPL from the interstitial spaces surrounding myocytes and adipocytes into the capillary lumen (7). In Gpihbp1 knockout mice (Gpihbp1 Ϫ/Ϫ ), LPL cannot reach the capillary lumen and therefore remains mislocalized within the interstitial spaces surrounding myocytes and adipocytes (7). Because LPL is absent from capillaries in Gpihbp1 Ϫ/Ϫ mice, the plasma triglyceride levels in those mice are extremely high (8), similar to those in mice with a complet...

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Section: Discussionmentioning

confidence: 99%

Unexpected Expression Pattern for Glycosylphosphatidylinositol-anchored HDL-binding Protein 1 (GPIHBP1) in Mouse Tissues Revealed by Positron Emission Tomography Scanning

Olafsen

Young

Davies

et al. 2010

Journal of Biological Chemistry

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“…Our in vitro study also showed that the addition of A peptide to the culture medium suppresses LPL activity and expression in 3T3-L1 cells 18) . In adipocytes, the LPL gene is regarded as a target gene of PPAR-gamma 11,29) ; therefore, A may downregulate LPL expression and production through the suppression of PPAR-gamma in adipocytes. On the other hand, pioglitazone treatment in this study increased the LPL mass, consistent with a previous report 10) .…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Decreases Plasma Angiotensin II Concentration inType 2 Diabetes

Saiki

Ohira

Endo

et al. 2010

JAT

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Aim:Adipocytes express all components of the renin-angiotensin system (RAS), and adipocyte RAS regulates adipocyte differentiation and metabolism. Plasma angiotensin (A ) is a putative marker of adipocyte RAS production. The aim of this study was to investigate the effect of pioglitazone on plasma A in type 2 diabetes (T2D). Methods: Fifty Japanese subjects with T2D were randomly allocated to two groups. One group was administered pioglitazone 30 mg/day (pioglitazone group) and the other group was not given pioglitazone (control group) for 16 weeks. Lipoprotein lipase mass in preheparin serum (LPL mass) was measured as an adipocyte-derived factor and a marker of insulin sensitivity. Results: In the pioglitazone group, the mean HbA1c decreased ( p 0.0001), LPL mass increased ( p 0.0001), and plasma A decreased ( p 0.0007), whereas these parameters were unchanged in the control group. The change in plasma A correlated negatively with the change in LPL mass (r 0.312) in the pioglitazone group. In the pioglitazone group, the decrease in plasma A was higher ( p 0.0002) and the increase in LPL mass tended to be higher ( p 0.0941) in the subgroup with higher baseline plasma A than that with lower plasma A . Conclusions: The present study indicates that pioglitazone decreases plasma A associated with an increase in LPL mass in T2D. The insulin-sensitizing effect of pioglitazone may be involved in suppressing adipocyte RAS. J Atheroscler Thromb, 2010; 17:651-657.

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“…'251-labelled lipoprotein lipase was prepared by the lactoperoxidase method and was separated from unreacted iodide and from any damaged protein by chromatography on heparin-Sepharose, as previously described (Wallinder et al, 1984). Human apo CII and apo CIII were purified from plasma (BengtssonOlivecrona and Olivecrona, 1991).…”

Section: Methodsmentioning

confidence: 99%

Chymotryptic cleavage of lipoprotein lipase

Lóokene

Bengtsson‐Olivecrona

1993

European Journal of Biochemistry

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Treatment of bovine lipoprotein lipase (LPL) with chymotrypsin results in cleavage between residues Phe390-Ser391 and between Trp392-Sa393, indicating that this region is exposed in the native conformation of LPL. Two main fragments are generated, one large including the aminoterminus (chymotrypsin-truncated LPL = c-LPL) and one small, carboxy-terminal fragment. The small fragment is not stable, but is further degraded by the protease. Isolated c-LPL has full catalytic activity against tributyryl glycerol (tributyrin) and p-nitrophenyl butyrate, while the activity against emulsions of long-chain triacylglycerols and against liposomes is reduced and the activity against milk fat globules and chylomicrons is lost. Several. properties of c-LPL were investigated. It was found that c-LPL interacts with apolipoprotein CII (apo CII) as efficiently as intact LPL. The truncated enzyme bound to liposomes and to emulsions of long-chain triacylglycerols as well as the intact enzyme did. In contrast, c-LPL did not bind to milk fat globules or to chylomicrons. The activity of c-LPL was more sensitive to inhibition by other lipid-binding proteins, e.g. apolipoprotein CIII (apo CIII), than was the intact enzyme. The affinity for heparin was as high with c-LPL as with intact LPL. Like intact LPL, c-LPL is dimeric in its active form, as evidenced by sucrose density gradient centrifugation.It is concluded that the reduced catalytic and lipid-binding properties of c-LPL compared with intact LPL are related to the properties of the substrate interface. It is speculated that the carboxyterminal part of LPL contains a secondary lipid-binding site, which is important for activity against chylomicrons and related substrates.

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Hepatic and extrahepatic uptake of intravenously injected lipoprotein lipase

Cited by 112 publications

References 20 publications

Unexpected Expression Pattern for Glycosylphosphatidylinositol-anchored HDL-binding Protein 1 (GPIHBP1) in Mouse Tissues Revealed by Positron Emission Tomography Scanning

Unexpected Expression Pattern for Glycosylphosphatidylinositol-anchored HDL-binding Protein 1 (GPIHBP1) in Mouse Tissues Revealed by Positron Emission Tomography Scanning

Pioglitazone Decreases Plasma Angiotensin II Concentration inType 2 Diabetes

Chymotryptic cleavage of lipoprotein lipase

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