| Type I diabetes mellitus decreases in vivo macrophage-to-feces reverse cholesterol transport despite increased biliary sterol secretion in mice. | |
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MedLine Citation:
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PMID: 22180634 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Type I diabetes mellitus (T1DM) increases atherosclerotic cardiovascular disease, while the underlying pathophysiology is still incompletely understood. We investigated whether experimental T1DM impacts HDL-mediated reverse cholesterol transport (RCT). C57BL/6J mice with alloxan-induced T1DM had higher plasma cholesterol levels (P<0.05), particularly within HDL, and increased hepatic cholesterol content (P<0.001). T1DM resulted in increased bile flow (2.1-fold; P<0.05) and biliary secretion of bile acids (BA, 10.5-fold; P<0.001), phospholipids (4.5-fold; P<0.001), and cholesterol (5.5-fold; P<0.05). Hepatic cholesterol synthesis was unaltered, while BA synthesis was increased in T1DM (P<0.001). Mass fecal BA output was significantly higher in T1DM mice (1.5-fold; P<0.05), fecal neutral sterol excretion did not change due to increased intestinal cholesterol absorption (2.1-fold; P<0.05). Overall in vivo macrophage-to-feces RCT, using [3H]cholesterol-loaded primary mouse macrophage foam cells, was 20% lower in T1DM (P<0.05), mainly due to reduced tracer excretion within BA (P<0.05). In vitro experiments revealed unchanged cholesterol efflux towards T1DM HDL, while SR-BI-mediated selective uptake from T1DM HDL was lower in vitro and in vivo (HDL kinetic experiments) (P<0.05), conceivably due to increased glycation of HDL-associated proteins (+65%, P<0.01). In summary, despite higher mass biliary sterol secretion T1DM impairs macrophage-to-feces RCT, mainly by decreasing hepatic selective uptake, a mechanism conceivably contributing to increased cardiovascular disease in T1DM. |
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Authors:
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Jan Freark de Boer; Wijtske Annema; Marijke Schreurs; Jelske N van der Veen; Markus van der Giet; Niels Nijstad; Folkert Kuipers; Uwe J F Tietge |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-18 |
Journal Detail:
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Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University Medical Center Groningen, Netherlands; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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