| Reduced absorption of saturated fatty acids and resistance to diet-induced obesity and diabetes by ezetimibe-treated and Npc1l1-/- mice. | |
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MedLine Citation:
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PMID: 18718999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The impact of NPC1L1 and ezetimibe on cholesterol absorption are well documented. However, their potential consequences relative to absorption and metabolism of other nutrients have been only minimally investigated. Thus studies were undertaken to investigate the possible effects of this protein and drug on fat absorption, weight gain, and glucose metabolism by using Npc1l1(-/-) and ezetimibe-treated mice fed control and high-fat, high-sucrose diets. Results show that lack of NPC1L1 or treatment with ezetimibe reduces weight gain when animals are fed a diabetogenic diet. This resistance to diet-induced obesity results, at least in part, from significantly reduced absorption of dietary saturated fatty acids, particularly stearate and palmitate, since food intake did not differ between groups. Expression analysis showed less fatty acid transport protein 4 (FATP4) in intestinal scrapings of Npc1l1(-/-) and ezetimibe-treated mice, suggesting an important role for FATP4 in intestinal absorption of long-chain fatty acids. Concomitant with resistance to weight gain, lack of NPC1L1 or treatment with ezetimibe also conferred protection against diet-induced hyperglycemia and insulin resistance. These unexpected beneficial results may be clinically important, given the focus on NPC1L1 as a target for the treatment of hypercholesterolemia. |
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Authors:
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Eric D Labonté; Lisa M Camarota; Juan C Rojas; Ronald J Jandacek; Dean E Gilham; Joanna P Davies; Yiannis A Ioannou; Patrick Tso; David Y Hui; Philip N Howles |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-08-21 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 295 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-16 Completed Date: 2008-11-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G776-83 Citation Subset: IM |
Affiliation:
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Dept. of Pathology, Genome Research Institute, Univ. of Cincinnati, 2120 E. Galbraith Rd., Cincinnati, OH 45237, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azetidines / pharmacology* Diabetes Mellitus / etiology*, prevention & control Dietary Carbohydrates / administration & dosage* Dietary Fats / administration & dosage* Fatty Acid Transport Proteins / biosynthesis Fatty Acids / metabolism* Female Hyperglycemia / prevention & control Intestinal Absorption / physiology* Male Membrane Transport Proteins / deficiency*, physiology Mice Obesity / prevention & control* |
| Grant Support | |
ID/Acronym/Agency:
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R01DK76907/DK/NIDDK NIH HHS; R01HL78900/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Azetidines; 0/Dietary Carbohydrates; 0/Dietary Fats; 0/Fatty Acid Transport Proteins; 0/Fatty Acids; 0/Membrane Transport Proteins; 0/Npc1l1 protein, mouse; 0/Slc27a4 protein, mouse; 163222-33-1/ezetimibe |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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