| Author: | Wu, Tin Wan |
| Title: | The impact of declined adipocyte MDM2 in aged subcutaneous white adipose tissue (sWAT) on non-alcoholic fatty liver disease (NAFLD) |
| Advisors: | Cheng, K. Y. Kenneth (HTI) |
| Degree: | M.Sc. |
| Year: | 2022 |
| Subject: | Adipose tissues Fatty liver Liver -- Diseases Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | vii, 42, 40 pages : color illustrations |
| Language: | English |
| Abstract: | Introduction: Previous studies have revealed that adipose tissue will be greatly declined in extremely old age, while on the contrary, senescent cell accumulation in adipose tissue will be increased. This phenomenon is found to be closely related to metabolic diseases, for instance, type 2 diabetes and non-alcoholic fatty liver disease. Therefore, exploring the pathogenesis between ageing adipose tissue and metabolic disorders has become the research goal of current studies. Especially for the research on subcutaneous white adipose tissue (sWAT), which itself is beneficial to protect against metabolic complications, is of important research value. This study aims to explore the causal relationship between adipose tissue and the liver in metabolic diseases. Moreover, to go deeper into the topic, this study also aims to investigate whether diminished MDM2 in aged sWAT has an association with the development of NAFLD. Aims: Objective 1: Exploring the causal relationship between aged sWAT and liver in metabolic diseases. Objective 2: Investigating the impact of diminished MDM2 (in sWAT) on the development or progression of NAFLD. Method: To evaluate the impact of aged sWAT on the liver in metabolic diseases, a specific sWAT-MDM2-KO mouse model was used to mimic the condition of sWAT during aging. The senescence status of sWAT was analyzed using Immunohistochemistry (IHC) staining of p21 and confirmed by qPCR of p21. While the liver situation was assessed by qPCR, histopathology staining, and IHC staining. Results: Senescence was observed in the sWAT of both the control and the KO mice. However, the level of senescence was similar in those two experimental groups. Normal size and number of adipocytes were found in the Cre-injected mice. Compared to the control mice with NAFLD development, sWAT-MDM2-KO mice seem to prevent the development of NAFLD. There were also no inflammation and fibrosis conditions identified. Conclusion: Although the expression of MDM2 dramatically decreased in the KO mice, the expression of p53 was not affected. Therefore, the senescence status of sWAT in the KO mice was not as severe as expected. Furthermore, KO mice showed normal lipid handling ability as the fatty liver was not observed in the KO mice but found in the control mice. A reasonable explanation of this phenomenon is the presence of compensation by the other lipid handling tissue, such as the liver. It seems that MDM2 gene knockout in sWAT would prevent the development of NAFLD. However, follow-up experiments are required to confirm the finding to rule out random errors caused by the small sample size. |
| Rights: | All rights reserved |
| Access: | restricted access |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 6535.pdf | For All Users (off-campus access for PolyU Staff & Students only) | 15.67 MB | Adobe PDF | View/Open |
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