| Unexpected effects of fasting on murine lipid homeostasis--transcriptomic and lipid profiling. | |
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MedLine Citation:
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PMID: 20347175 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND & AIMS: Starvation induces massive perturbations in metabolic pathways involved in energy metabolism, but its effect on the metabolism of lipids, particularly cholesterol, is little understood. METHODS: A comparative genomic analysis of the gut and the liver in response to fasting was performed, with intestinal perfusion and lipid profiling of the plasma, bile, liver, intestinal tissue, perfusate, and faeces in FVB mice. RESULTS: The expression profiles suggested increased cholesterol trafficking in the liver and decreased trafficking in the small intestine. Plasma cholesterol concentrations significantly increased, and triglycerides decreased in fasting. Surprisingly, in prolonged fasting, the biliary bile salt and lipid output rates increased, with increased hepatic and intestinal lipid turnover, and enhanced trans-intestinal cholesterol excretion. In contrast, faecal sterol loss declined sharply. To investigate whether the increased biliary phospholipid secretion could nourish the intestinal epithelium, we studied the histology of the small intestines upon fasting in multidrug resistant protein 2 deficient mice with scarce biliary phospholipids. Their adaptive biliary response to fasting was lost, while the shortage of biliary phospholipids strongly induced apoptosis and proliferation in the small intestine and increased the number of mucin-producing cells. CONCLUSION: Even with no dietary fat, lipid levels remain remarkably constant in the murine liver and intestines during prolonged fasting. The biliary system, always assumed to be coupled to the postprandial response, shows a paradoxical increase in activity. We hypothesise that biliary lipids are mobilised to supply the enterocytes with luminal fuel and to stabilise transport systems in the intestine for ensuring a rapid recovery when the food supply resumes. |
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Authors:
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Milka Sokolović; Aleksandar Sokolović; Cindy P A A van Roomen; Anna Gruber; Roelof Ottenhoff; Saskia Scheij; Theodorus B M Hakvoort; Wouter H Lamers; Albert K Groen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-04 |
Journal Detail:
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Title: Journal of hepatology Volume: 52 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-03 Completed Date: 2010-08-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 737-44 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Medical Biochemistry, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. m.sokolovic@amc.uva.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Division Cholesterol / metabolism Comparative Genomic Hybridization Fasting / physiology* Gene Expression Profiling* Homeostasis Immunohistochemistry Intestine, Small / cytology, physiology Intestines / physiology Lipids / physiology* Liver / physiology Male Mice Mice, Inbred Strains Mice, Knockout Mucins / biosynthesis, genetics P-Glycoproteins / deficiency, genetics Phospholipids / metabolism Receptors, G-Protein-Coupled / genetics Sterols / metabolism Triglycerides / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Lipids; 0/Mucins; 0/P-Glycoproteins; 0/P-glycoprotein 2; 0/Phospholipids; 0/Receptors, G-Protein-Coupled; 0/SREB2 protein, mouse; 0/Sterols; 0/Triglycerides; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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