Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
| dc.contributor.advisor | Zhu, Yuyan (FSN) | en_US |
| dc.creator | Liu, Qing | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/14295 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | en_US |
| dc.rights | All rights reserved | en_US |
| dc.title | The role of cholesterol esterification in adipocyte expandability and its associated metabolic disorders | en_US |
| dcterms.abstract | Obesity is characterized by the excessive expansion of adipose tissue, while cholesterol homeostasis is important for maintaining adipose tissue function. Among the regulators of cholesterol homeostasis, SOAT1 is the key enzyme responsible for converting free cholesterol into cholesteryl ester in adipocytes. However, the role of cholesterol esterification in regulating adipocyte expandability remains unclear. Here, we investigated the role of SOAT1 in regulating adipogenesis and cholesterol homeostasis within adipocytes, as well as the physiological function of SOAT1 in mature adipocytes. A positive correlation between the expression pattern of SOAT1 in adipose tissue and adiposity in both murine and human was observed, suggesting a potential role of SOAT1 in adipose tissue expansion. Supportively, SOAT1 was found to be essential for adipogenesis, but not for adipocyte hypertrophy in vitro. We found SOAT1 deficiency alters cholesterol trafficking and distribution within adipocytes, leading to impaired maturation of SREBP2. Notably, the adipogenic capacity of SOAT1-deficient preadipocytes could be restored by enhancing the transcription of PPARĪ³ or SREBP1, as well as through the addition of specific nutritional factors, like oleic acid and high cholesterol. These results demonstrated an important role of SOAT1 in maintaining cholesterol homeostasis and adipogenesis in adipocytes. | en_US |
| dcterms.abstract | To examine the physiological functions of SOAT1 in mature adipocytes, we generated adipocyte-specific SOAT1-knockout (AKO) mice by crossing Adiponecin-Cre mice with SOAT1 flox/flox mice. SOAT1 flox/flox mice were used as control (CTRL) ones. | en_US |
| dcterms.abstract | To investigate the importance of SOAT1 in adipocytes in response to excessive exogenous cholesterol overload, we employed a high cholesterol diet treatment for those mice. We found the AKO mice displayed elevated energy expenditure and browning in the iWAT even under normal room temperature conditions compared to CTRL. Furthermore, the ATGL protein level were enhanced in iWAT of AKO mice. Consistently, we knockout SOAT1 in vitro also exhibited a similar phenotype. These findings suggest that SOAT1 may play a crucial role in promoting WAT beiging through ATGL-mediated enhanced lipolysis. | en_US |
| dcterms.abstract | To investigate the adipocyte-SOAT1 function during obesity development, we employed a high fat high cholesterol diet with normal diet as control. Under HFHC feeding, AKO mice exhibited little impact on BW and fat mass, however it demonstrated a decreased non-alcoholic fatty liver disease (NAFLD) severity phenotype. Furthermore, echocardiography revealed a significant decrease in heart function parameters and an increase of heart mass in AKO mice. These findings suggested the participation of adipocyte-SOAT1 in the crosstalk between adipose tissue and distant organs. Under ND feeding, AKO mice exhibited increased fat mass as well as adipocyte size compared with CTRL. This pro-adiposity effect of SOAT1 deficiency was observed as early as 8-week old. These findings indicate the adipocyte-SOAT1 may engage in the adipose tissue development at early stage. | en_US |
| dcterms.abstract | In summary, our study has elucidated the important role of SOAT1 as a regulator in maintaining cholesterol distribution and adipogenesis in vitro, as well as activating WAT thermogenesis in vivo under HCD feeding. The process of cholesterol esterification plays a critical role in adipose tissue expansion and overall metabolic health. | en_US |
| dcterms.extent | 189 pages : color illustrations | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2023 | en_US |
| dcterms.educationalLevel | Ph.D. | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.LCSH | Cholesterol -- Metabolism | en_US |
| dcterms.LCSH | Esterification | en_US |
| dcterms.LCSH | Adipose tissues | en_US |
| dcterms.LCSH | Hong Kong Polytechnic University -- Dissertations | en_US |
| dcterms.accessRights | open access | en_US |
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