The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD
Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/142227 |
| _version_ | 1811696357318066176 |
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| author | Chen, Jiapeng Zhuang, Yan Sng, Ming Keat Tan, Nguan Soon Wahli, Walter |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Chen, Jiapeng Zhuang, Yan Sng, Ming Keat Tan, Nguan Soon Wahli, Walter |
| author_sort | Chen, Jiapeng |
| collection | NTU |
| description | Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68+ or bone marrow-derived CD11b+ Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d-/- mouse liver revealed that FSP1 is expressed in CD11b+ Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d-/- livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d-/- livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid β-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD. |
| first_indexed | 2024-10-01T07:38:05Z |
| format | Journal Article |
| id | ntu-10356/142227 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:38:05Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1422272023-02-28T16:57:51Z The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD Chen, Jiapeng Zhuang, Yan Sng, Ming Keat Tan, Nguan Soon Wahli, Walter School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Pparb/d FSP1 Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68+ or bone marrow-derived CD11b+ Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d-/- mouse liver revealed that FSP1 is expressed in CD11b+ Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d-/- livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d-/- livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid β-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD. MOE (Min. of Education, S’pore) Published version 2020-06-17T08:06:23Z 2020-06-17T08:06:23Z 2019 Journal Article Chen, J., Zhuang, Y., Sng, M. K., Tan, N. S., & Wahli, W. (2019). The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD. International Journal of Molecular Sciences, 20(20), 5115-. doi:10.3390/ijms20205115 1661-6596 https://hdl.handle.net/10356/142227 10.3390/ijms20205115 31618976 2-s2.0-85073451362 20 20 en International Journal of Molecular Sciences © 2019 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf |
| spellingShingle | Science::Medicine Pparb/d FSP1 Chen, Jiapeng Zhuang, Yan Sng, Ming Keat Tan, Nguan Soon Wahli, Walter The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD |
| title | The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD |
| title_full | The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD |
| title_fullStr | The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD |
| title_full_unstemmed | The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD |
| title_short | The potential of the FSP1cre-Pparb/d-/- mouse model for studying juvenile NAFLD |
| title_sort | potential of the fsp1cre pparb d mouse model for studying juvenile nafld |
| topic | Science::Medicine Pparb/d FSP1 |
| url | https://hdl.handle.net/10356/142227 |
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