retinol-palmitate and Hypercholesterolemia

Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats.. Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks.. Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyltransferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet.. Chronic feeding of a vitamin A-enriched diet in hypercholesterolemic obese rats normalizes the plasma HDL-C level and presumably improves RCT, with an effective dose of 52 mg/kg diet. Further studies should focus on the pharmacological potential of vitamin A supplementation to correct an abnormal human obesity-associated lipoprotein metabolism.

Topics: Animals; Antioxidants; Biological Transport; Cholesterol; Diet; Diterpenes; Humans; Hypercholesterolemia; Liver; Male; Obesity; Rats; Rats, Mutant Strains; Retinyl Esters; Thinness; Vitamin A

Post-prandial lipoprotein kinetics were investigated in subjects who lack functioning low-density lipoprotein (LDL) receptors [homozygous familial hypercholesterolaemia (FH)].. An oral fat load was given, and chylomicron plasma kinetics was determined by monitoring the clearance of triglyceride, retinyl palmitate and apolipoprotein B48, calculated as the area under the curve, for 7.5 h. In addition, the binding and uptake of chylomicron remnants by fibroblasts of FH and control subjects were assessed in vitro.. Based on the plasma kinetics of chylomicron triglyceride, retinyl palmitate and apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be substantially delayed compared with normolipidaemic control subjects. Consistent with involvement of the LDL receptor in chylomicron clearance, binding and uptake of chylomicron remnants by fibroblasts of FH subjects was found to be substantially less than in cells from control subjects.. This study shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH and that the LDL receptor is significantly involved in the clearance of post-prandial lipoproteins. Moreover, this study raises the possibility that in FH, and in other disorders in which LDL receptor expression is reduced, atherogenesis might be a post-prandial disease.

Topics: Adolescent; Adult; Cells, Cultured; Chylomicrons; Diterpenes; Fibroblasts; Homozygote; Humans; Hypercholesterolemia; Lipoproteins; Middle Aged; Postprandial Period; Protein Binding; Retinyl Esters; Skin; Vitamin A

The authors evaluated serum retinol, retinol-binding protein (RBP), and beta-carotene levels to elucidate the retinoid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). The mean retinol levels by gender (1.83 mumol/L for females and 2.24 mumol/L for males) in diabetics were higher than those (1.31 mumol/L for females and 1.82 mumol/L for males) in control subjects (P < 0.0001, P < 0.01, respectively). The mean retinol/RBP ratios (0.95 for females and 0.97 for males) of diabetics were higher than those of the control subjects (0.60 for females and 0.64 for males) and of male patients having impaired glucose tolerance (0.55) (P < 0.0001). Lipid-lowering medication significantly decreased retinol, with decreasing apolipoprotein C-II but without a commensurate decrease in RBP. The retinol levels had a positive correlation with apolipoprotein C-II in all or normolipidemic patients with diabetes and control subjects. The high retinol/RBP ratio implies that an excessive or free retinol possibly exists in NIDDM. An alternative metabolism of retinol is inferred to underlie NIDDM without direct influences of cholesterol or triglyceride themselves.

Topics: Anticholesteremic Agents; Antioxidants; Apolipoprotein C-II; Apolipoprotein C-III; Apolipoproteins C; beta Carotene; Blood Glucose; Carotenoids; Cholesterol; Diabetes Mellitus, Type 2; Diterpenes; Female; Humans; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Retinol-Binding Proteins; Retinyl Esters; Sex Characteristics; Simvastatin; Triglycerides; Vitamin A