title: Chronic vitamin A-enriched diet feeding regulates hypercholesterolaemia through transcriptional regulation of reverse cholesterol transport pathway genes in obese rat model of WNIN/GR-Ob strain.
abstract: OBJECTIVE
  Hepatic scavenger receptor class B1 (SR-B1), a high-density lipoprotein (HDL) receptor, is involved in the selective uptake of HDL-associated esterified cholesterol (EC), thereby regulates cholesterol homoeostasis and improves reverse cholesterol transport. Previously, we reported in euglycaemic obese rats (WNIN/Ob strain) that feeding of vitamin A-enriched diet normalized hypercholesterolaemia, possibly through hepatic SR-B1-mediated pathway. This study was aimed to test whether it would be possible to normalize hypercholesterolaemia in glucose-intolerant obese rat model (WNIN/GR/Ob) through similar mechanism by feeding identical vitamin A-enriched diet.
  
  
  METHODS
  In this study, 30 wk old male lean and obese rats of WNIN/GR-Ob strain were divided into two groups and received either stock diet or vitamin A-enriched diet (2.6 mg or 129 mg vitamin A/kg diet) for 14 wk. Blood and other tissues were collected for various biochemical analyses.
  
  
  RESULTS
  Chronic vitamin A-enriched diet feeding decreased hypercholesterolaemia and normalized abnormally elevated plasma HDL-cholesterol (HDL-C) levels in obese rats as compared to stock diet-fed obese groups. Further, decreased free cholesterol (FC) and increased esterified cholesterol (EC) contents of plasma cholesterol were observed, which were reflected in higher EC to FC ratio of vitamin A-enriched diet-fed obese rats. However, neither lecithin-cholesterol acyltransferase (LCAT) activity of plasma nor its expression (both gene and protein) in the liver were altered. On the contrary, hepatic cholesterol levels significantly increased in vitamin A-enriched diet fed obese rats. Hepatic SR-B1 expression (both mRNA and protein) remained unaltered among groups. Vitamin A-enriched diet fed obese rats showed a significant increase in hepatic low-density lipoprotein receptor mRNA levels, while the expression of genes involved in HDL synthesis, namely, ATP-binding cassette protein 1 (ABCA1) and apolipoprotein A-I, were downregulated. No such response was seen in vitamin A-supplemented lean rats as compared with their stock diet-fed lean counterparts.
  
  
  CONCLUSIONS
  Chronic vitamin A-enriched diet feeding decreased hypercholesterolaemia and normalized HDL-C levels, possibly by regulating pathways involved in HDL synthesis and degradation, independent of hepatic SR-B1 in this glucose-intolerant obese rat model.
authors.affiliation: Division of Lipid Biochemistry, National Institute of Nutrition, Hyderabad, India.
authors.forename: Shanmugam M
authors.initials: SM
authors.lastname: Jeyakumar
authors.affiliation: Division of Lipid Biochemistry, National Institute of Nutrition, Hyderabad, India.
authors.forename: Alex
authors.initials: A
authors.lastname: Sheril
authors.affiliation: Division of Lipid Biochemistry, National Institute of Nutrition, Hyderabad, India.
authors.forename: Ayyalasomayajula
authors.initials: A
authors.lastname: Vajreswari
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000097:blood* / Q000235:genetics; D008076:Cholesterol, HDL / Q000096:biosynthesis / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000178:diet therapy / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009765:Obesity / Q000097:blood* / Q000178:diet therapy / Q000235:genetics; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis* / Q000235:genetics; D014801:Vitamin A / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D002784:Cholesterol; D008076:Cholesterol, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D051122:Scavenger Receptors, Class B; D014801:Vitamin A; C577834:Abca1 protein, rat; C495125:Scarb1 protein, rat