Composition and metabolism of very low density lipoproteins in dog cardiaclymph

1981 ◽  
Vol 59 (8) ◽  
pp. 709-714 ◽  
Author(s):  
P. Julien ◽  
A. Angel

In the present study, very low density lipoprotein (VLDL, d < 1.006) in cardiac lymph was characterized to determine its role as a metabolic substrate in the interstitial compartment. A major efferent cardiac lymph trunk was cannulated in fasting (18 h) dogs (20–27 kg). Three to five millilitres of lymph were collected over 3–4 h at 4 °C. Cardiac lymph VLDL concentration was 1.7 ± 0.7 mg protein∙100 mL−1 compared with 1.8 ± 0.8 mg protein∙100 mL−1 in plasma. The VLDL triglyceride concentration in lymph was 1.0 ± 0.3 mg triglyceride∙100 mL−1 with triglyceride/protein ratio of 0.9 compared with plasma VLDL triglyceride of 5.0 ± 1.6 mg∙100 mL−1 with a triglyceride/protein ratio of 5.5. Electron microscopy of VLDL revealed globular particles with a mean diameter of 388 Å in lymph and 661 Å in plasma. Thus, cardiac lymph VLDL are smaller and contain less triglyceride per particle than plasma VLDL. Following i.v. administration of human 125I-labelled low density lipoprotein ([125I]LDL, d 1.025–1.045), cardiac lymph/plasma LDL specific activity ratio was 0.52 ± 0.15 (n = 3) and 0.55 ± 0.15 (n = 4) at 3 and 27 h, respectively. The fact that the specific activity ratio did not reach 1 at plateau suggests continuous addition of unlabelled LDL in the cardiac interstitium, presumably from VLDL precursors. These findings demonstrate that on a protein basis the concentration of VLDL in cardiac lymph equals that of plasma, and also suggests that VLDL degradation and LDL production occur in the cardiac interstitial space.

1978 ◽  
Vol 176 (1) ◽  
pp. 169-174 ◽  
Author(s):  
P Thomopoulos ◽  
M Berthelier ◽  
D Lagrange ◽  
M J Chapman ◽  
M H Laudat

The effect of human plasma lipoproteins on lipogenesis from glucose has been studied in isolated rat adipocytes. The very-low-density lipoproteins increased lipogenesis specifically, whereas low-density lipoproteins and high-density lipoproteins were without effect. Such stimulation could be reproduced with partially delipidated very-low-density lipoproteins. Nod-esterified fatty acids and glycerol were also without effect. Pretreatment of the adipocytes with trypsin did not alter the effect of very-low-density lipoprotein. The presence of Ca2+ was required for the full activation of lipogenesis. The synthesis of acylglycerol fatty acids and of acylglycerol glycerol were equally increased. The effect of very-low-density lipoprotein was not additive to that of insulin. It is suggested that very-low-density lipoprotein may directly stimulate lipogenesis in fat-cells, particularly in states when the lipoproteins are present at high concentration in the circulation.


1981 ◽  
Vol 198 (2) ◽  
pp. 373-377 ◽  
Author(s):  
A D Kalopissis ◽  
S Griglio ◽  
M I Malewiak ◽  
R Rozen ◽  
X L Liepvre

The very-low-density-lipoprotein secretion rate of isolated hepatocytes obtained from rats fed a high-fat diet was half that of cells from control animals. In fat-fed rats, the initial cellular uptake of [l-14C]oleate in vitro was decreased by 25%, its esterification to triacylglycerols and phospholipids by 50% and its incorporation into very-low-density-lipoprotein triacylglycerols by 70%. Exogenous oleate was not the main precursor of very-low-density lipoproteins in these animals. Lipogenesis, a minor source of very-low-density lipoproteins with the control diet in our experimental conditions, was inhibited by 84% after fat-feeding. A short-term inhibition of lipogenesis in vitro did not result in a decrease in very-low-density-lipoprotein secretion rate. The results suggest that fat-feeding decreased availability of exogenous as well as endogenous fatty acids for synthesis of very-low-density lipoproteins.


1985 ◽  
Vol 227 (2) ◽  
pp. 529-536 ◽  
Author(s):  
A C Rustan ◽  
J ∅ Nossen ◽  
T Berg ◽  
C A Drevon

Primary cultures of rat hepatocytes were used to study secretion of very-low-density lipoproteins and metabolism of asialofetuin. The ionophore monensin inhibited both secretion of very-low-density lipoproteins and binding and degradation of asialofetuin in a concentration-dependent manner. Secretion as well as receptor binding were markedly decreased after 15 min treatment with monensin. The inhibitory effect of the ionophore was fully reversible, and no effect on protein synthesis was observed at concentrations up to 50 microM. The secretion of apoproteins (B-small, B-large and E) and that of albumin were inhibited to the same extent as was triacylglycerol secretion. Secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin than was the metabolism of asialofetuin. Maximum inhibition of very-low-density-lipoprotein secretion was obtained at 5-10 microM-monensin, whereas 25 microM was required to obtain maximum inhibition of binding and degradation of asialofetuin. The number of surface receptors for asialofetuin decreased to about half when the cells were exposed to 25 microM-monensin. It is possible that monensin inhibits endo- and exo-cytosis via a similar mechanism, e.g. by disturbing proton gradients. Since secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin, it is likely that monensin independently inhibits endocytic and secretory functions in cultured hepatocytes.


1981 ◽  
Vol 59 (8) ◽  
pp. 637-641 ◽  
Author(s):  
G. Steiner ◽  
W. K. Ilse

These studies examine the mechanisms responsible for the heterogeneous nature of very low density lipoprotein (VLDL) triglyceride production. The fasting dog has been used as a model to follow the incorporation of [2-3H]glycerol and [1-14C]palmitate into the triglyceride of VLDL isolated from plasma and from mesenteric lymph. The former represents mainly hepatic VLDL, and the latter, intestinal VLDL. VLDL from each source has been subfractionated into Sf 100–400, Sf 60–100, and Sf 20–60 components. The plateau in triglyceride specific activity achieved during constant infusions of the labelled precursors was higher in small VLDL than in large VLDL. This indicates that the small VLDL triglyceride is not derived exclusively from that in large VLDL. This applies to both hepatic and intestinal VLDL. This contrasts with apolipoprotein B in small VLDL, which other studies show to be entirely derived from large VLDL. Thus both the liver and the intestine incorporate triglyceride into particles whose density extends through the entire VLDL spectrum. Unless triglyceride-rich lipoproteins with the density of VLDL but with no apolipoprotein B are produced, these data raise the possibility that triglyceride may enter VLDL directly.


1973 ◽  
Vol 51 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Abraham I. Kook ◽  
David Rubinstein

The synthesis and secretion by perfused rat liver of the lipid and protein moieties of the α- and β-lipoprotein-containing components of the very low density lipoproteins was studied, following additions of [3H]palmitate and [14C]leucine to the perfusate. The lipid moieties of both components became labelled early in the perfusion, and had a pattern of labelling similar to that of their protein moieties. The protein of the α-lipoprotein component became labelled at the same time as the lipid. The appearance of the isotope in the β-lipoprotein component was delayed, but it then surpassed that of the α-lipoprotein component in both total radioactivity and specific activity. From these data a working hypothesis has been developed which suggests that the protein but not the lipid of the β-lipoprotein component is incorporated into very low density lipoprotein in the sequence in which it is synthesized, while the α-lipoprotein component is drawn randomly from a large pool.


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