Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Articles Article Faculty Publications -Articles Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Inhibiting extracellular cathepsin d reduces hepatic steatosis in spraguedawley rats y Subject The topic of the resource Extracellular cathepsin D; Lysosomal enzyme; NAFLD; Small-molecule inhibitor Description An account of the resource Dietary and lifestyle changes are leading to an increased occurrence of non-alcoholic fatty liver disease (NAFLD). Using a hyperlipidemic murine model for non-alcoholic steatohepatitis (NASH), we have previously demonstrated that the lysosomal protease cathepsin D (CTSD) is involved with lipid dysregulation and inflammation. However, despite identifying CTSD as a major player in NAFLD pathogenesis, the specific role of extracellular CTSD in NAFLD has not yet been investigated. Given that inhibition of intracellular CTSD is highly unfavorable due to its fundamental physiological function, we here investigated the impact of a highly specific and potent small-molecule inhibitor of extracellular CTSD (CTD-002) in the context of NAFLD. Treatment of bone marrow-derived macrophages with CTD-002, and incubation of hepatic HepG2 cells with a conditioned medium derived from CTD-002-treated macrophages, resulted in reduced levels of inflammation and improved cholesterol metabolism. Treatment with CTD-002 improved hepatic steatosis in high fat diet-fed rats. Additionally, plasma levels of insulin and hepatic transaminases were significantly reduced upon CTD-002 administration. Collectively, our findings demonstrate for the first time that modulation of extracellular CTSD can serve as a novel therapeutic modality for NAFLD. 2019 by the authors. Creator An entity primarily responsible for making the resource Khurana P.; Yadati T.; Goyal S.; Dolas A.; Houben T.; Oligschlaeger Y.; Agarwal A.K.; Kulkarni A.; Shiri-Sverdlov R. Source A related resource from which the described resource is derived Biomolecules, Vol-9, No. 5 Publisher An entity responsible for making the resource available MDPI AG Date A point or period of time associated with an event in the lifecycle of the resource 2019-01-01 Identifier An unambiguous reference to the resource within a given context <a href="https://doi.org/10.3390/biom9050171" target="_blank" rel="noreferrer noopener">https://doi.org/10.3390/biom9050171</a> <br /><br /><a href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065657807&amp;doi=10.3390%2Fbiom9050171&amp;partnerID=40&amp;md5=4ed83ff470ab325398420e7137ce9fde" target="_blank" rel="noreferrer noopener">https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065657807&amp;doi=10.3390%2fbiom9050171&amp;partnerID=40&amp;md5=4ed83ff470ab325398420e7137ce9fde</a> Rights Information about rights held in and over the resource All Open Access; Gold Open Access; Green Open Access Relation A related resource ISSN: 2218273X; PubMed ID: 31060228 Format The file format, physical medium, or dimensions of the resource Online Language A language of the resource English Type The nature or genre of the resource Article Coverage The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant Khurana P., Aten Porus Lifesciences Pvt Ltd., Bengaluru, 560068, Karnataka, India; Yadati T., Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, ER 6229, Netherlands; Goyal S., Aten Porus Lifesciences Pvt Ltd., Bengaluru, 560068, Karnataka, India; Dolas A., Aten Porus Lifesciences Pvt Ltd., Bengaluru, 560068, Karnataka, India; Houben T., Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, ER 6229, Netherlands; Oligschlaeger Y., Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, ER 6229, Netherlands; Agarwal A.K., Department of Chemistry, CHRIST (Deemed to be University), Bengaluru, 560029, Karnataka, India; Kulkarni A., Aten Porus Lifesciences Pvt Ltd., Bengaluru, 560068, Karnataka, India, Avaliv Therapeutics, Naples, 34120, FL, United States; Shiri-Sverdlov R., Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, ER 6229, Netherlands