| Normal intestinal dietary fat and cholesterol absorption, intestinal apolipoprotein B (ApoB) mRNA levels, and ApoB-48 synthesis in a hypobetalipoproteinemic kindred without any ApoB truncation. | |
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MedLine Citation:
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PMID: 9284903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this study was to characterize intestinal apolipoprotein B (apoB) metabolism in subjects with familial hypobetalipoproteinemia (FHBL), where segregation analysis supports linkage to the apoB gene but no apoB truncations are present. We investigated cholesterol and fat absorption, intestinal apoB mRNA synthesis and editing, as well as apoB-48 synthesis. Plasma triglycerides (TG) and retinyl palmitate in the chylomicron fractions were analyzed after 12 hours of fasting and then repeatedly for 14 hours after ingestion of a vitamin A-containing high-fat meal. Cholesterol absorption was assessed using a dual stable-isotope method. Mean peak times and concentrations and areas under the curve (AUCs) for fat absorption and mean percentages of cholesterol absorption were comparable in affected and nonaffected family members. Intestinal biopsies were extracted for total RNA and also incubated with 35S-methionine for measurements of apoB synthesis. Similar quantities of apoB mRNA were found to be expressed in the intestine in affected and control subjects by RNase protection assay. ApoB mRNA editing assay showed that the majority of apoB-100 mRNA was edited to the apoB-48 form to a similar extent in both groups. Virtually no apoB-100 protein was synthesized by the intestine in any subject, and apoB-48 protein synthesis was not significantly different in the affected individuals. These data are consistent with in vivo metabolism data that show normal production rates for liver-derived apoB-100 but increased apoB-100 fractional catabolic rates in affected members of this family. Thus, the molecular defect probably does not affect transcription, translation, or secretion of apoB-containing lipoproteins, but may instead affect their clearance. |
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Authors:
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J I Pulai; M Averna; R A Srivastava; M A Latour; R E Clouse; R E Ostlund; G Schonfeld |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Metabolism: clinical and experimental Volume: 46 ISSN: 0026-0495 ISO Abbreviation: Metab. Clin. Exp. Publication Date: 1997 Sep |
Date Detail:
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Created Date: 1997-10-03 Completed Date: 1997-10-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0375267 Medline TA: Metabolism Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1095-100 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Absorption Adult Aged Apolipoprotein B-48 Apolipoproteins B / biosynthesis*, genetics* Cholesterol, Dietary / pharmacokinetics* Dietary Fats / pharmacokinetics* Eating / physiology Female Humans Hypobetalipoproteinemias / genetics*, metabolism Intestines / metabolism* Lipids / blood Male Middle Aged RNA Editing* RNA, Messenger / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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5P60DK20579/DK/NIDDK NIH HHS; HLR0142460/HL/NHLBI NIH HHS; MO1RR00036/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein B-48; 0/Apolipoproteins B; 0/Cholesterol, Dietary; 0/Dietary Fats; 0/Lipids; 0/RNA, Messenger |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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