Apo B metabolism in the cynomolgus monkey: evidence for post-transcriptional regulation.
Previous studies have shown that hepatic apo B mRNA levels do not increase in animals fed high cholesterol diets, even though plasma apo B concentrations increase markedly. As a result, it has been suggested that the diet-induced increase in plasma apo B levels was due solely to an inhibited clearance of those lipoproteins. The present study was undertaken to test that hypothesis. Hepatic apo B mRNA levels were measured in liver biopsies taken from five male cynomolgus monkeys before and twice after, they began to consume a high cholesterol diet. The diet had no effect on hepatic apo B mRNA levels, even though it caused a 7-fold increase in the plasma apo B levels. However, measurements of the apo B secretion rate in eight separate monkeys (four chow-fed and four cholesterol-fed) by isotope dilution showed that apo B secretion by the liver was increased 4-fold in the cholesterol-fed monkeys. These data, taken together, indicate that apo B secretion is not regulated by the rate at which the apo B gene is transcribed, but at some point further along in the secretion pathway.
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Metabolic Diseases Research and Molecular Biology Research, Upjohn Company, Kalamazoo, MI 49001.
Castle
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Murray
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Funk
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Hunt
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Marotti
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Melchior
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D000595:Amino Acid Sequence; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D001483:Base Sequence; D002791:Cholesterol, Dietary / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D005786:Gene Expression Regulation; D006937:Hypercholesterolemia / Q000139:chemically induced; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D008657:Metabolic Clearance Rate; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*
D001055:Apolipoproteins B; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008074:Lipoproteins; D012333:RNA, Messenger