UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

9-2-2015

Document Type

Article

Disciplines

Cellular and Molecular Physiology | Digestive System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Molecular Biology | Nutritional and Metabolic Diseases

Abstract

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.

Rights and Permissions

Citation: Int J Mol Sci. 2015 Sep 2;16(9):21056-69. doi: 10.3390/ijms160921056. Link to article on publisher's site

DOI of Published Version

10.3390/ijms160921056

Comments

© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

Related Resources

Link to Article in PubMed

Keywords

NAFLD, metabolic syndrome, cyclodextrin, electron microscopy, lysosomes

Journal/Book/Conference Title

International journal of molecular sciences

PubMed ID

26404254

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

 
 

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