Regulation of polyunsaturated fat induced postprandial hypercholesterolemia by a novel gene Phc-2.
Inbred mouse strains vary in susceptibility or resistance to dietary induced atherosclerosis. To investigate the effect of polyunsaturated fat feeding on postprandial serum cholesterol levels, in C57BL/67 (B6) and BALB/cJ inbred mice, we fed by stomach gavage previously fasted mice, a mixture containing 30% sunflower oil, 5% cholesterol, 2% sodium cholate and 0.5% choline chloride. The most significant difference in serum cholesterol levels between B6 and BALB/cJ mouse strains was observed at 2 h postfeeding. Susceptible B6 strain mice had a 41% postprandial increment in serum cholesterol. The resistant BALB/cJ strain had an insignificant 16% rise in serum cholesterol, at 2 h. We next examined eight other inbred mouse strains, to identify the gene(s) that regulate the observed 2 h postprandial hypercholesterolemia response, in the susceptible B6 mouse strain. Only the C57BR/cdJ and C57L/J strains developed postprandial hypercholesterolemia, at 2 h. The C57BR/cdJ strain had a 20% increase and the C57L/J strain a 62% increase in postprandial serum cholesterol levels. From this result, we found that the postprandial hypercholesterolemic response to an acute polyunsaturated fat-cholesterol feed, cosegregated with the a allele at the Gpd-1 and Ahd-1 loci, on mouse chromosome 4. In this study, non-responsiveness cosegregated with the b allele at the Gpd-1 and Ahd-1 loci. Thus polyunsaturated fat-cholesterol induced postprandial hypercholesterolemia appeared to be genetically determined by a gene located between the Gpd-1 and Ahd-1 loci, in mice. The putative gene regulating polyunsaturated fat-cholesterol induced post-absorptive hypercholesterolemia was designated Phc-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Vaithilingam
D S
DS
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
Antao
V
V
Kakis
G
G
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002874:Chromosome Mapping; D002875:Chromosomes; D002878:Chromosomes, Human, Pair 1; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D002791:Cholesterol, Dietary; D004042:Dietary Fats, Unsaturated; D002784:Cholesterol