The metabolic conversion of very-low-density lipoprotein into low-density lipoprotein by the extrahepatic tissues of the rat

Abstract

1. The work reported was designed to provide quantitative information about the capacity of the extrahepatic tissues of the rat to degrade injected VLD lipoproteins (very-lowdensity lipoproteins, d< 1.006) to LD lipoproteins (low-density lipoproteins, d 1.006-1.063) and to study the fate of the different VLD-lipoprotein apoproteins during the degradative process. 2. Rat liver VLD lipoproteins, radioactively labelled in their protein moieties, were produced by the perfusion of the organ and were either injected into the circulation of the supradiaphragmatic rats or incubated in rat plasma at 370C. At a time (75 min) when approx. 90% of the triacylglycerol of the VLD lipoproteins had been hydrolysed, the supradiaphragmatic rats were bled and VLD lipoproteins, LD lipoproteins and HD lipoproteins (high-density lipoproteins, d 1.063-1.21) were separated from their plasma and from the plasma incubated in vitro. The apoproteins of each of the lipoprotein classes were resolved by gel-filtration chromatography into three main fractions, designated peaks I, II and III. 3. Incubation of the liver VLD lipoproteins in plasma in vitro led to the transfer of about 30 % of the total protein radioactivity to the HD lipoproteins. This transfer mainly involved the peak-II (arginine-rich and/or apo A-I) and peak-Ill (apo C) proteins. There was also a small transfer of radioactivity (about 5 % of the total) to the LD lipoproteins. 4. Injection of the liver VLD lipoproteins into the circulation of the supradiaphragmatic rat resulted in the transfer of about 15 % of the total VLD-lipoprotein radioactivity to the LD lipoproteins. This transfer involved mainly the peak-I (apo B) proteins and accounted for about 20% of the total apo B protein radioactivity of the injected VLD lipoproteins. When the endogenous plasma VLD lipoprotein was taken into account the transfer of apo B protein was about 35 %.5. The transfer of peak-Il protein radioactivity from the VLD to the HD lipoproteins was greater in the plasma of the supradiaphragmatic rat than in the incubated plasma, suggesting that there was a net transfer of peak-II apoproteins during the VLD lipoprotein degradation. The transfer of peak-III protein radioactivity was not greater in the plasma of the supradiaphragmatic rat, but there was a loss of this radioactivity from the circulation.

Effects of insulin on the disposal of 14C-labelled very low density lipoprotein triglycerides in intact and hepatectomized rats

“…This finding may be important in view of present evidence that hyperinsulinaemia is a risk factor for atherosclerosis [24]. In functionally hepatectomized rats, the appearance of 14C-lipids in plasma IDL and LDL + HDL after administration of 14C-VLDL-triglycerides demonstrates the capacity of the rat to degrade VLDL to lipoproteins of higher density without the intervention of the liver, in agreement with Suri et al [25]. The conversion of VLDL to IDL is catalyzed by the action of extrahepatic lipoprotein lipase [26], releasing non-esterified fatty acid (NEFA) from the hydrolysis of VLDL-triglycerides which are taken up by the subjacent tissue.…”

Nascent very-low-density lipoprotein triacylglycerol hydrolysis by lipoprotein lipase is inhibited by apolipoprotein E in a dose-dependent manner

“…After cannulation of the portal vein with an Abbocath-T cannule (26G*19 mm ; Abbott Laboratories, Queenborough, Kent, U.K.), livers were isolated surgically and perfused (1.5 ml\min) in itro in a recycling fashion as described previously for rats [19,20] with some minor modifications. Briefly, the liver and perfusate were maintained at 37 mC throughout the experiment.…”

Cholesterol Transport through the Plasma

“…Against the view that the liver is necessary for the conversion of remnants into LDL, Dory et al 1561 have shown that the isolated perfused rat heart is capable of converting VLDL into LDL, and Suri et al 1571 have reported the formation of an LDL-like lipoprotein from VLDL in functionally hepatectomized rats. Deckelbaum et al 1581 have also shown that the hydrolysis of human VLDL by milk lipoprotein lipase in vitro results in the formation of a cholesteryl-ester-rich lipoprotein resembling LDL.…”