Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways
Nonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH in...
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13272 |
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| author | Noriko Suzuki‐Kemuriyama Akari Abe Sae Nakane Kinuko Uno Shuji Ogawa Atsushi Watanabe Ryuhei Sano Megumi Yuki Katsuhiro Miyajima Dai Nakae |
| author_facet | Noriko Suzuki‐Kemuriyama Akari Abe Sae Nakane Kinuko Uno Shuji Ogawa Atsushi Watanabe Ryuhei Sano Megumi Yuki Katsuhiro Miyajima Dai Nakae |
| author_sort | Noriko Suzuki‐Kemuriyama |
| collection | DOAJ |
| description | Nonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline‐deficient, methionine‐lowered, l‐amino acid‐defined high‐fat diet (CDAHFD). CDAHFD with insufficient methionine induced insulin sensitivity and enhanced NASH pathology, but without obesity. In contrast, CDAHFD with sufficient methionine induced steatosis, and unlike CDAHFD with insufficient methionine, also induced obesity and insulin resistance. Gene profile analysis revealed that the disease severity in CDAHFD may partially be due to upregulation of the Rho family GTPases pathway and mitochondrial and nuclear receptor signal dysfunction. The signaling factors/pathways detected in this study may assist in future study of NASH regulation, especially its ‘nonobese’ subtype. |
| first_indexed | 2024-12-19T17:55:23Z |
| format | Article |
| id | doaj.art-1f1412a381574fb1a0fe5dffddcb28a0 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-19T17:55:23Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-1f1412a381574fb1a0fe5dffddcb28a02022-12-21T20:11:50ZengWileyFEBS Open Bio2211-54632021-11-0111112950296510.1002/2211-5463.13272Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathwaysNoriko Suzuki‐Kemuriyama0Akari Abe1Sae Nakane2Kinuko Uno3Shuji Ogawa4Atsushi Watanabe5Ryuhei Sano6Megumi Yuki7Katsuhiro Miyajima8Dai Nakae9Department of Nutritional Science and Food Safety Faculty of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Food and Nutritional Science Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Food and Nutritional Science Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Graduate School of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Faculty of Applied Bioscience Tokyo University of Agriculture Setagaya JapanDepartment of Nutritional Science and Food Safety Faculty of Applied Bioscience Tokyo University of Agriculture Setagaya JapanNonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline‐deficient, methionine‐lowered, l‐amino acid‐defined high‐fat diet (CDAHFD). CDAHFD with insufficient methionine induced insulin sensitivity and enhanced NASH pathology, but without obesity. In contrast, CDAHFD with sufficient methionine induced steatosis, and unlike CDAHFD with insufficient methionine, also induced obesity and insulin resistance. Gene profile analysis revealed that the disease severity in CDAHFD may partially be due to upregulation of the Rho family GTPases pathway and mitochondrial and nuclear receptor signal dysfunction. The signaling factors/pathways detected in this study may assist in future study of NASH regulation, especially its ‘nonobese’ subtype.https://doi.org/10.1002/2211-5463.13272nonalcoholic steatohepatitis‘nonobese’ NASH subtypeRho GTPases signaling |
| spellingShingle | Noriko Suzuki‐Kemuriyama Akari Abe Sae Nakane Kinuko Uno Shuji Ogawa Atsushi Watanabe Ryuhei Sano Megumi Yuki Katsuhiro Miyajima Dai Nakae Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways FEBS Open Bio nonalcoholic steatohepatitis ‘nonobese’ NASH subtype Rho GTPases signaling |
| title | Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways |
| title_full | Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways |
| title_fullStr | Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways |
| title_full_unstemmed | Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways |
| title_short | Nonobese mice with nonalcoholic steatohepatitis fed on a choline‐deficient, l‐amino acid‐defined, high‐fat diet exhibit alterations in signaling pathways |
| title_sort | nonobese mice with nonalcoholic steatohepatitis fed on a choline deficient l amino acid defined high fat diet exhibit alterations in signaling pathways |
| topic | nonalcoholic steatohepatitis ‘nonobese’ NASH subtype Rho GTPases signaling |
| url | https://doi.org/10.1002/2211-5463.13272 |
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