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IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2′,3′,5′‐tri‐acetyl‐N6‐(3‐hydroxylaniline) adenosine (IMM‐H007) can eliminate hepatic steatosis in hamsters fed...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586352/ https://www.ncbi.nlm.nih.gov/pubmed/28904866 http://dx.doi.org/10.1002/2211-5463.12272 |
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author | Shi, Huijie Wang, Qingchun Yang, Liu Xie, Shouxia Zhu, Haibo |
author_facet | Shi, Huijie Wang, Qingchun Yang, Liu Xie, Shouxia Zhu, Haibo |
author_sort | Shi, Huijie |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2′,3′,5′‐tri‐acetyl‐N6‐(3‐hydroxylaniline) adenosine (IMM‐H007) can eliminate hepatic steatosis in hamsters fed a high‐fat diet (HFD), as a model of NAFLD. Compared with HFD‐only controls, IMM‐H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, (1)H‐MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM‐H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM‐H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo, IMM‐H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM‐H007 resolves hepatic steatosis in HFD‐fed hamsters by the regulation of lipid metabolism. Thus, IMM‐H007 has therapeutic potential for NAFLD. |
format | Online Article Text |
id | pubmed-5586352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55863522017-09-13 IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet Shi, Huijie Wang, Qingchun Yang, Liu Xie, Shouxia Zhu, Haibo FEBS Open Bio Research Articles Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2′,3′,5′‐tri‐acetyl‐N6‐(3‐hydroxylaniline) adenosine (IMM‐H007) can eliminate hepatic steatosis in hamsters fed a high‐fat diet (HFD), as a model of NAFLD. Compared with HFD‐only controls, IMM‐H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, (1)H‐MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM‐H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM‐H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo, IMM‐H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM‐H007 resolves hepatic steatosis in HFD‐fed hamsters by the regulation of lipid metabolism. Thus, IMM‐H007 has therapeutic potential for NAFLD. John Wiley and Sons Inc. 2017-08-29 /pmc/articles/PMC5586352/ /pubmed/28904866 http://dx.doi.org/10.1002/2211-5463.12272 Text en © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Shi, Huijie Wang, Qingchun Yang, Liu Xie, Shouxia Zhu, Haibo IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
title | IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
title_full | IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
title_fullStr | IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
title_full_unstemmed | IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
title_short | IMM‐H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
title_sort | imm‐h007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high‐fat diet |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586352/ https://www.ncbi.nlm.nih.gov/pubmed/28904866 http://dx.doi.org/10.1002/2211-5463.12272 |
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