Postprandial lipemia. A key for the conversion of high density lipoprotein2 into high density lipoprotein3 by hepatic lipase.

Patsch, Josef R.; Prasad, Sarada C.; Gotto, Antonio M.; Bengtsson‐Olivecrona, Gunilla

doi:10.1172/jci111624

Cited by 251 publications

(100 citation statements)

References 18 publications

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“…Formation of HDLz from HDL3 may result from several events : the transfer of surface constituents (free cholesterol, PdtCho and apo C) released during the lipolysis of triacylglycerol-rich lipoprotein [33], their further metabolism by the LCAT reaction which generates cholesteryl esters [34] and the possible involvement of the cholesteryl ester transfer proteins [35]. The reverse conversion of HDL2 to HDL3 is more obscure, although several arguments suggest a role for the hepatic triglyceride lipase (H-TGL), acting on HDL2 phospholipid [ l l , 13, 151.…”

Section: Discussionmentioning

confidence: 99%

“…The in vitro degradation of HDLz phospholipid by the isolated enzyme was also described [6 -81 and this hydrolysis was further reported to affect the HDLz-HDL3 distribution [15]. For others, the HDLz ---t HDL, interconversion would take place through the action of hepatic lipase on triacylglycerol-enriched HDLz [3], such as the HDLz obtained during experimental post-prandial hyperlipemia [16], or in vitro, following repeated incubations of HDLz with VLDL and 'neutral lipid exchange proteins' [17]. In this scheme, the hydrolysis of the acquired triacylglycerol in HDL would operate a reduction of the particle core volume [3].…”

Section: Human High-density Lipoproteins Hdlzmentioning

confidence: 99%

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Distribution of high-density lipoprotein 2 and 3 constituents during in vitro phospholipid hydrolysis

et al. 1987

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Human high-density lipoproteins HDLzHighly purified phospholipase Az from Crotulus adurnanteus allowed gradual degrees of lipolysis (30-90%) on both HDL2 and HDL3. Moderate phospholipid hydrolyses were achieved using hepatic triacylglycerol lipase, partially purified from post-heparin plasma. Moreover, the latter enzyme seemed to exert a lysophospholipase activity, acting on the 2-acyl-sn-glycero-3-phosphocholine generated. A purified sphingomyelinase C from Staphylococcus aureus was also used and completely hydrolysed HDL sphingomyelin.2. After incubation, doubly labelled HDLz/HDL3 were reisolated in their appropriate density interval. In the presence of albumin, which bound most of the lipolysis products, phospholipolysis induced a phospholipid depletion of the particles and a heterogeneous partition of all HDLz constituents between the HDL, and HDL3 density intervals. Radioactivity distributions correlated with mass movements. The 'HDL3-like' particles isolated after HDLz lipolysis were twice as rich in cholesterol as plasma HDL3. No loss of apoprotein A , was recorded due to phospholipolysis. In the absence of albumin, the density distributions of HDLz or HDL3 constituents were unaffected by phospholipolysis, the products of lipolysis being reisolated with the stable particles.3. Control and treated HDL were also reisolated by equilibrium density gradient ultracentrifugation, gel chromatography or by gradient gel electrophoresis. Phospholipase treatment in the presence of albumin induced a shift of the HDLz or HDL3 whole distribution towards particles of higher density and lower apparent size. Lipolysed HDL, thus showed characteristics intermediate between those of HDLz and HDL3.So, phospholipolysis may affect the physical parameters of HDL particles, but additional pathways such as cholesterol movements and apoprotein loss must be linked to achieve the HDLz 4 HDL3 interconversion.In human plasma, high-density lipoproteins (HDL) represent a wide spectrum of particles in which two main subfractions are usually distinguished by a variety of procedures:HDLz and HDL3 [l-31. These two subfractions differ in chemical composition, apoprotein content, size, density and also in their metabolic behaviours. For instance, and as regards phospholipid hydrolysis, HDL3 is a good substrate for lecithin -cholesterol acyltransferase (LCAT), a reaction which favours the uptake of peripheral cell cholesterol, while HDLz reacts very poorly [4, 51. On the other hand, HDLz is preferentially hydrolysed, compared to HDL3, by the hepatic Correspondence to B . P. Perret,

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Section: Discussionmentioning

confidence: 99%

Section: Human High-density Lipoproteins Hdlzmentioning

confidence: 99%

Distribution of high-density lipoprotein 2 and 3 constituents during in vitro phospholipid hydrolysis

et al. 1987

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“…Two fractions were obtained by pooling appropriate volume contents of the rotor (Beckman TI-14): firstly, lipoprotein fractions with an S f higher than 200 corresponding mainly to chylomicrons/remnants; and secondly, a fraction with an S f of between 20 and 200 corresponding mainly to VLDL/ remnants. The zonally isolated lipoproteins were concentrated by pressure filtration using Amicon cells and subsequently purified further by gel filtration using Sepharose 2B with PBS as an eluent buffer [29]. Purity of TGRL fractions was confirmed by gel electrophoresis using lipoprotein fractionation gels.…”

Section: Methodsmentioning

confidence: 99%

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

et al. 2005

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Aims/hypothesis: Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL/remnants and chylomicrons/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance. Methods: We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity, glucose uptake, insulin signalling and intramyocellular lipid (IMCL) content using fully differentiated L6 skeletal muscle cells. Results: Incubation with TGRLs diminished insulin-stimulated glycogen synthesis, glycogen synthase activity, glucose uptake and insulin-stimulated phosphorylation of Akt and glycogen synthase kinase 3. Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1-and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. The overall observed effects were time-and dose-dependent and paralleled IMCL accumulation. NEFA concentration in the incubation media did not increase in the presence of TGRLs indicating that the effects observed were solely due to intact lipoprotein particles. Moreover, co-incubation of TGRLs with orlistat, a potent active-site inhibitor of various lipases, did not alter TGRL-induced effects, whereas co-incubation with receptor-associated protein (RAP), which inhibits interaction of TGRL particles with members of the LDL receptor family, reversed the TGRL-induced effects on glycogen synthesis and insulin signalling. Conclusions/ interpretation: Our data suggest that the accumulation of TGRLs in the blood stream of insulin-resistant patients may not only be a consequence of insulin resistance but could also be a cause for it.

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“…However, this effect could very well be desireable in obesity and type 2 diabetes; in both conditions plasma triglyceride levels are frequently increased accompanied with CETPmediated loss of HDL-cholesterol. 10,11 In both situations, leptin and insulin levels are high reducing PLTP and CETP levels and consequently loss of HDL cholesterol.…”

Section: Leptin and Insulin On Lipid Transfer Proteins S Kaser Et Almentioning

confidence: 99%

“…6,7 CETP catalyzes the transfer of cholesteryl esters (CE) from HDL to apoB-containg lipoproteins in exchange for triglycerides 8,9 resulting in the conversion of larger to smaller particles and low HDL cholesterol levels. 10,11 Thus, both PLTP and CETP stimulate several critical steps of reverse cholesterol transport.…”

Section: Introductionmentioning

confidence: 99%

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2

et al. 2001

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AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones -the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP. METHODS: PLTP activity and CETP concentration -measured by exogenous substrate assay and enzyme-linked immunosorbent assay -were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis. RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin. CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

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Postprandial lipemia. A key for the conversion of high density lipoprotein2 into high density lipoprotein3 by hepatic lipase.

Cited by 251 publications

References 18 publications

Distribution of high-density lipoprotein 2 and 3 constituents during in vitro phospholipid hydrolysis

Distribution of high-density lipoprotein 2 and 3 constituents during in vitro phospholipid hydrolysis

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2

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