Vitamin A-enriched Diet Modulates Reverse Cholesterol Transport in Hypercholesterolemic Obese Rats of the WNIN/Ob Strain

Abstract

Aim: 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. Methods: 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. Results: 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. Conclusions: 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.

Linear association of compound dietary antioxidant index with hyperlipidemia: a cross-sectional study

“…The vitamins (A, D, and E) and carotenoids in CDAI are fat-soluble and vitamin C is water-soluble, which is relevant for absorption, transport and action. Feeding a VA-rich (52 mg/kg) diet for 20 weeks in hypercholesterolemic obese rats increased plasma lecithin cholesterol acyltransferase activity and expression of ATP-binding cassette transporter protein A1, which, in turn, led to normalization of plasma HDL-C levels ( 43 ). Vitamin C (VC) is an essential nutrient for humans and the effect of administration is highly dose dependent ( 44 ), maximizing neutrophil concentration, reducing ROS production and inhibiting LDL-C oxidation through dietary intake ( 45 , 46 ).…”

All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling

“…ey compared the serum levels of vitamin A in 110 patients with severe obesity with that in 58 healthy people and found that the levels of vitamin A in obese patients were significantly lower than those in the healthy controls [38]. Studies found that feeding fat rats with a vitamin A-supplemented diet could correct insulin resistance, plasma high-density lipoprotein level, and hypercholesterolemia in obese rats [39,40]. In addition, the role of retinoic acid in inhibiting adipogenesis in vitro was confirmed in 3T3-L1 cells [41].…”

Impact of Dietary Lipids on the Reverse Cholesterol Transport: What We Learned from Animal Studies

“…Dietary supplementation with either low (52 mg/kg) or high (129 mg/kg) doses of vitamin A affected several players in RCT in obese rats [ 173 ]. Both hepatic SR-BI and ABCA1 proteins were increased in the liver, a dual effect resulting in a decrease of circulating HDL.…”