Proopiomelanocortin (POMC) is a polypeptide precursor with 241 amino acid residues which undergoes extensive post-translational modification to yield a range of smaller, biological active peptides including £\-, £] -, £^-melanocyte-stimulating hormone (£\-MSH, £]-MSH, £^-MSH )¡A£]-endorphin (£]-EP) and adrenocorticotrophic hormone (ACTH). POMC-derived peptides play important roles in appetite and energy homeostasis. Recently, the peripheral POMC system is under active investigation to delineate their pathogenic roles in metabolic diseases such as Cushing¡¦s syndrome and obesity. In the present study, we utilized adenovirus gene delivery system to achieve systemic POMC overexpression in adult C57/BL6 mice for at least 30 days. Subsequently, the plasma and abdominal adipose tissue of mice were collected and analyzed by biochemical assays and weight determination respectively. POMC overexpression did not increase in the food uptake and body weight. These results imply that local POMC gene delivery induced the visceral fat accumulation and altered the metabolism in mice. It was observed that systemic POMC overexpression significantly elevated the triglyceride and the cholesterol levels in mice. However, POMC gene delivery also induced elevated plasma glucose concentration at weeks 1-4 and evoked glucose tolerance in mice at week 4. Interestingly, insulin resistance was readily detected in POMC-transduced in mice at as early as week 1. Besides, Micro-CT scanning and histological studies demonstrated that the visceral fat was significantly increased in POMC over-expressing mice compared with control animals. These data indicate that hepatic POMC gene delivery causes systemic ACTH rise and insulin resistance, which recapitulates the clinical features of Cushing¡¦s syndrome. In summary, POMC gene delivery induces systemic POMC overexpression and results in visceral fat accumulation and insulin resistance, which may facilitates a mice model for Cushing¡¦s-like metabolic syndrome.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0216111-175425 |
| Date | 16 February 2011 |
| Creators | Tang, Chia-Hua |
| Contributors | Pei-Wen Wang, Ming-Hong Tai, Lee-Wei Chen |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0216111-175425 |
| Rights | withheld, Copyright information available at source archive |
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