Weekly Treatment of 2-Hydroxypropyl-β-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice
| Autor: | Steven W.M. Olde Damink, Alena Grebe, Dieter Lütjohann, Tom Houben, Ronit Shiri-Sverdlov, Fons Verheyen, Nathalie Vaes, Sofie M. A. Walenbergh, Ger H. Koek, Eicke Latz, Patrick J. van Gorp, Tim Hendrikx, Mike L. J. Jeurissen |
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| Přispěvatelé: | Moleculaire Genetica, Moleculaire Celbiologie, Surgery, Interne Geneeskunde, RS: NUTRIM - R2 - Gut-liver homeostasis, RS: CARIM - R2 - Cardiac function and failure, RS: GROW - Oncology, Genetica & Celbiologie, Pathologie, MUMC+: MA Maag Darm Lever (9), RS: GROW - R2 - Basic and Translational Cancer Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
HOMEOSTASIS
RESISTANT cytology [Liver] metabolism [Lysosomes] STEATOHEPATITIS lcsh:Chemistry metabolism [Kupffer Cells] chemistry.chemical_compound Mice genetics [Receptors LDL] drug effects [Lysosomes] lcsh:QH301-705.5 Spectroscopy Mice Knockout drug therapy [Hyperlipidemias] pharmacology [beta-Cyclodextrins] Reverse cholesterol transport beta-Cyclodextrins General Medicine Computer Science Applications 2-Hydroxypropyl-beta-cyclodextrin drug effects [Liver] administration & dosage [beta-Cyclodextrins] Cholesterol Liver Low-density lipoprotein ddc:540 Cholesteryl ester lipids (amino acids peptides and proteins) Cholesterol storage medicine.medical_specialty Kupffer Cells CYCLODEXTRIN OVERCOMES Injections Subcutaneous LOW-DENSITY-LIPOPROTEIN Hyperlipidemias Biology Catalysis Article metabolic syndrome Drug Administration Schedule Inorganic Chemistry lysosomes INFLAMMATION drug effects [Kupffer Cells] Internal medicine NAFLD medicine metabolism [Hyperlipidemias] Animals deficiency [Receptors LDL] Physical and Theoretical Chemistry Liver X receptor Molecular Biology EVERY ORGAN FATTY LIVER-DISEASE ACCUMULATION electron microscopy Organic Chemistry genetics [Hyperlipidemias] metabolism [Cholesterol] medicine.disease TRANSPORT Disease Models Animal Endocrinology chemistry lcsh:Biology (General) lcsh:QD1-999 cyclodextrin Receptors LDL Steatohepatitis metabolism [Liver] Lipoprotein |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 16, Iss 9, Pp 21056-21069 (2015) International journal of molecular sciences, 16(9), 21056-21069. Multidisciplinary Digital Publishing Institute (MDPI) Volume 16 Issue 9 Pages 21056-21069 International journal of molecular sciences 16(9), 21056-21069 (2015). doi:10.3390/ijms160921056 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms160921056 |
| Popis: | Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-beta-cyclodextrin (HP-B-CD) is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs). Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr(-/-)) mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice treated with HP-B-CD demonstrated a shift in intracellular cholesterol distribution towards cytoplasmic cholesteryl ester (CE) storage and a decrease in cholesterol crystallization inside KCs. Compared to untreated hyperlipidemic mice, the foamy KC appearance and liver cholesterol remained similar upon HP-B-CD administration, while hepatic campesterol and 7alpha-hydroxycholesterol levels were back increased. Thus, HP-B-CD could be a useful tool to improve intracellular cholesterol levels in the context of the metabolic syndrome, possibly through modulation of phyto- and oxysterols, and should be tested in the future. Additionally, these data underline the existence of a shared etiology between lysosomal storage diseases and NAFLD. |
| Databáze: | OpenAIRE |
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