2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The endothelial dysfunction blocker CU06-1004 ameliorates choline-deficient L-amino acid diet-induced non-alcoholic steatohepatitis in mice

      research-article
      1 , 2 , 1 , *
      PLoS ONE
      Public Library of Science

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Non-alcoholic steatohepatitis (NASH) is a severe, advanced form of non-alcoholic fatty liver disease (NAFLD) that is associated with features of metabolic syndrome and characterized by hepatic steatosis, inflammation, and fibrosis. In addition, NASH is associated with endothelial dysfunction within the hepatic vasculature. Treatment with CU06-1004 (previously called Sac-1004) ameliorates endothelial dysfunction by inhibiting hyperpermeability and inflammation. In this study, we investigated the protective effects of CU06-1004 in a choline-deficient L-amino acid (CDAA)-induced mouse model of NASH for 3 or 6 weeks. Specifically, we evaluated the effects of CU06-1004 on lipid accumulation, inflammation, hepatic fibrosis, and liver sinusoidal endothelial cell (LSEC) capillarization through biochemical analysis, immunohistochemistry, and real-time PCR. We found that the administration of CU06-1004 to mice improved liver triglyceride (TG) and serum alanine aminotransferase (ALT) in this CDAA-induced model of NASH for 6 weeks. In groups of NASH induced mice for both 3 and 6 weeks, CU06-1004 significantly reduced the hepatic expression of genes related to lipogenesis, inflammation, and cell adhesion. However, expression of genes related to hepatic fibrosis and vascular endothelial changes were only decreased in animals with mild NASH. These results suggest that the administration of CU06-1004 suppresses hepatic steatosis, inflammation, fibrosis, and LSEC capillarization in a CDAA-induced mouse model of NASH. This suggests that CU06-1004 has therapeutic potential for the treatment of mild NASH.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: found
          • Article: not found

          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION

              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

              Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Methodology
                Role: Funding acquisitionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 December 2020
                2020
                : 15
                : 12
                : e0243497
                Affiliations
                [1 ] Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
                [2 ] CURACLE Co., Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea
                Faculty of Medicine & Health Science, UNITED ARAB EMIRATES
                Author notes

                Competing Interests: CURACLE Co, Ltd., provided support for the study in the form of salary for HZ, and provided the CU06-1004 sample. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                https://orcid.org/0000-0002-1534-2455
                Article
                PONE-D-20-16193
                10.1371/journal.pone.0243497
                7717513
                33275637
                973f4660-02f0-4545-9ca2-ba94b74f9096
                © 2020 Bae et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 May 2020
                : 20 November 2020
                Page count
                Figures: 5, Tables: 1, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: 2019R1C1C1003754
                Award Recipient :
                Funded by: National Research Foundation of Korea (KR)
                Award ID: 2019R1A2C3007142
                Award Recipient :
                CURACLE Co, Ltd., provided support for the study in the form of salary for HZ, and provided the CU06-1004 sample. The specific roles of this author are articulated in the ‘author contributions’ section. Funding was received from National Research Foundation of Korea (NRF) for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Model Organisms
                Mouse Models
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Animal Models
                Mouse Models
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Biology and Life Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Immunology
                Immune Response
                Inflammation
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Inflammation
                Biology and Life Sciences
                Nutrition
                Diet
                Medicine and Health Sciences
                Nutrition
                Diet
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Anatomical Pathology
                Cytopathology
                Steatosis
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Cytokines
                Biology and Life Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Medicine and Health Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Biology and Life Sciences
                Developmental Biology
                Molecular Development
                Cytokines
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Liver Fibrosis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article