Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice[S]
| العنوان: | Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice[S] |
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| المؤلفون: | Theo H. van Dijk, Anna Bertolini, Albert K. Groen, Henkjan J. Verkade, Johan W. Jonker, Ivo P van de Peppel |
| المساهمون: | Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Experimental Vascular Medicine, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition |
| المصدر: | Journal of Lipid Research, Vol 60, Iss 9, Pp 1562-1572 (2019) Journal of Lipid Research, 60(9), 1562-1572. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC Journal of lipid research, 60(9), 1562-1572. American Society for Biochemistry and Molecular Biology Inc. J Lipid Res |
| بيانات النشر: | Elsevier, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, 030204 cardiovascular system & hematology, transintestinal cholesterol excretion, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, ABSORPTION, Intestinal Mucosa, Research Articles, Mice, Knockout, Symporters, biology, Reabsorption, REDUCES ATHEROSCLEROSIS, intestinal cholesterol absorption, PLASMA-CHOLESTEROL, BILE-ACID TRANSPORT, Cholesterol, Intestinal cholesterol absorption, Female, lipids (amino acids, peptides, and proteins), medicine.drug, ezetimibe, medicine.medical_specialty, INHIBITION, Organic Anion Transporters, Sodium-Dependent, QD415-436, METABOLISM, Excretion, 03 medical and health sciences, Ezetimibe, Internal medicine, medicine, Animals, Liver X receptor, SLC10A2, NEUTRAL STEROL EXCRETION, Biological Transport, Cell Biology, ASBT inhibition, Sterol, Mice, Inbred C57BL, MICE, 030104 developmental biology, Intestinal Absorption, chemistry, biology.protein, LIVER-X-RECEPTOR |
| الوصف: | Transintestinal cholesterol excretion (TICE) is a major route for eliminating cholesterol from the body and a potential therapeutic target for hypercholesterolemia. The underlying mechanism, however, is largely unclear, and its contribution to cholesterol disposal from the body is obscured by the counteracting process of intestinal cholesterol reabsorption. To determine the quantity of TICE independent from its reabsorption, we studied two models of decreased intestinal cholesterol absorption. Cholesterol absorption was inhibited either by ezetimibe or, indirectly, by the genetic inactivation of the intestinal apical sodium-dependent bile acid transporter (ASBT; SLC10A2). Both ezetimibe treatment and Asbt inactivation virtually abrogated fractional cholesterol absorption (from 46% to 4% and 6%, respectively). In both models, fecal neutral sterol excretion and net intestinal cholesterol balance were considerably higher than in control mice (5- and 7-fold, respectively), suggesting that, under physiological conditions, TICE is largely reabsorbed. In addition, the net intestinal cholesterol balance was increased to a similar extent but was not further increased when the models were combined, suggesting that the effect on cholesterol reabsorption was already maximal under either condition alone. On the basis of these findings, we hypothesize that the inhibition of cholesterol (re)absorption combined with stimulating TICE will be most effective in increasing cholesterol disposal. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0022-2275 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::734da4eecc9690a38ef9c96adccdea15Test http://www.sciencedirect.com/science/article/pii/S002222752032318XTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....734da4eecc9690a38ef9c96adccdea15 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00222275 |
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