Impaired very low-density lipoprotein-triglyceride catabolism in acute and chronic fructose-fed rats

1989 ◽  
Vol 256 (4) ◽  
pp. E559-E565 ◽  
Author(s):  
T. Hirano ◽  
J. C. Mamo ◽  
M. E. Poapst ◽  
A. Kuksis ◽  
G. Steiner

Very low-density lipoprotein (VLDL)-triglyceride (TG) catabolism was compared in rats given chow and either a 10% fructose (F) or 10% glucose (G) drinking solution for both acute (A) (16 h) and chronic (C) (14 days) periods. VLDL-TG were labeled in F and G donor rats using different isotopic forms of glycerol. A mixture of the VLDLs was injected into F and G recipients and the decline in plasma TG radioactivities used as a measure of clearance. VLDL-TG from F donors was cleared more slowly than VLDL-TG from G donors. In F recipients, the half-life of VLDL-TG from either F or G donors was longer than that in G fed recipients. VLDL from the AF group, had a lower apoprotein E-to-C apoprotein ratio (E/C) than VLDL from the AG group. VLDL from both F groups had a lower E/C than did that from control rats. The E/C negatively correlated with plasma VLDL-TG. CF and CG VLDL had elevated CIII0 and lower CIII3 levels compared with their respective A groups and controls. The ratio of VLDL apoprotein B100, B95, and B48 did not differ between treatments. AF and AG VLDL were larger and enriched in TG compared with control or the CF and CG groups. The saturated fatty acid-to-unsaturated fatty acid ratio in VLDL-TG was higher in the G groups and AF group compared with controls. The present study suggests that the E/C may be lowered as a result of F consumption, thereby contributing to the impairment in VLDL-TG removal.

1988 ◽  
Vol 255 (3) ◽  
pp. E236-E240 ◽  
Author(s):  
T. Hirano ◽  
J. Mamo ◽  
M. Poapst ◽  
G. Steiner

Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in rats maintained on either chow and water (control) or chow and a 10% carbohydrate drinking solution (fructose or glucose). The hexose solutions were available for an acute (16 h) or chronic (14 day) period. The acute fructose (AF), acute glucose (AG), and chronic fructose (CF) groups were hypertriglyceridemic (HTG) compared with control. Plasma TG concentration in chronic glucose (CG)-fed rats was similar to control. VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The fractional catabolic rate (FCR) was then determined by monitoring the clearance of plasma [3H]VLDL-TG in recipient animals. Donors and recipients were treated in an identical manner. AF and CF groups had an FCR significantly lower than rats given glucose for comparable periods. Both fructose groups and the AG group also had a lower FCR than control. In contrast, FCR in the CG group was significantly higher than controls. TG production rate (TGPR) in both AF and CF fed rats did not significantly differ from controls, suggesting that the HTG observed in these animals was solely from a catabolic defect. AG- and CG-treated glucose animals both had TGPR significantly higher than controls. Therefore, overproduction of VLDL-TG contributed to the HTG associated with this carbohydrate.


1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.


Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2169-2174 ◽  
Author(s):  
Wan Huang ◽  
Anantha Metlakunta ◽  
Nikolas Dedousis ◽  
Heidi K. Ortmeyer ◽  
Maja Stefanovic-Racic ◽  
...  

It is well established that leptin increases the sensitivity of carbohydrate metabolism to the effects of insulin. Leptin and insulin also have potent effects on lipid metabolism. However, the effects of leptin on the regulation of liver lipid metabolism by insulin have not been investigated. The current study addressed the effects of leptin on insulin-regulated hepatic very low-density lipoprotein (VLDL) metabolism in vivo in rats. A 90-min hyperinsulinemic/euglycemic clamp (4 mU/kg · min−1) reduced plasma VLDL triglyceride (TG) by about 50% (P < 0.001 vs. saline control). Importantly, a leptin infusion (0.2 μg/kg · min−1) in combination with insulin reduced plasma VLDL-TG by about 80% (P < 0.001 vs. insulin alone). These effects did not require altered skeletal muscle lipoprotein lipase activity but did include differential effects of insulin and leptin on liver apolipoprotein (apo) B and TG metabolism. Thus, insulin decreased liver and plasma apoB100/B48 levels (∼50%, P < 0.01), increased liver TGs (∼20%, P < 0.05), and had no effect on fatty acid oxidation. Conversely, leptin decreased liver TGs (∼50%, P < 0.01) and increased fatty acid oxidation (∼50%, P < 0.01) but had no effects on liver or plasma apoB levels. Importantly, the TG-depleting and prooxidative effects of leptin were maintained in the presence of insulin. We conclude that leptin additively increases the suppressive effects of insulin on hepatic and systemic VLDL metabolism by stimulating depletion of liver TGs and increasing oxidative metabolism. The net effect of the combined actions of insulin and leptin is to decrease the production and TG content of VLDL particles.


2021 ◽  
Vol 2 (1) ◽  
pp. 15-24
Author(s):  
Murtadha M. Jawad

The present study was aimed efficiency to evaluate the unsaturated fatty acid omega-3 in reducing the side effects that resulted from the administration of cyclosporine drug in white rabbits. (60) white males' rabbits were used in this study, divided into four groups contain (15) rabbits per group and its subdivision into three groups (5) rabbits per group. The first group is orally administered with normal saline, the second group was administered cyclosporine (25mg/kg) only. Third groups were administered cyclosporine on the first day and omega-3 (500mg/kg) on the second day, while Fourth groups were administered cyclosporine on the first day and omega-3 (1000mg/kg) on the second day for periods (21,30,60) days respectively. After ending study periods, the animals were sacrificed and the blood was collected and the results were shown the following:  Administration with cyclosporine (25mg/kg)only and for periods were led to a significant increase(P<0.05) in total cholesterol, triglycerides and low-density lipoprotein(LDL) and a significant decrease(P<0.05) in high-density lipoprotein(HDL).whereas interaction with (500&1000mg/kg) of omega-3 and to all periods showed a significant decrease (p<0.05) in the total cholesterol, triglycerides and low-density lipoprotein(LDL) and significant decrease(p<0.05) in high-density lipoprotein(HDL), while the non-significant difference in high-density lipoprotein(HDL). This study concluded that omega-3 has an important role in reducing biochemistry side effects that result from the administration of cyclosporine drugs in white rabbits.


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