- Title
- The effect of Cannabis extract on the morphological and metabolic characteristics of various fat depots in diet-induced Obese and STZ-induced male wistar rats
- Creator
- Ramlugon, Sonaal
- Subject
- Rats as laboratory animals
- Subject
- Diabetes in practice
- Subject
- Cannabis -- South Africa
- Date Issued
- 2023-04
- Date
- 2023-04
- Type
- Doctoral theses
- Type
- text
- Identifier
- http://hdl.handle.net/10948/61282
- Identifier
- vital:70044
- Description
- To investigate the potential anti-diabetic/obesity properties of oral cannabis administration in an obese and streptozotocin (STZ)-induced diabetic rat model, as well as an obese rat model, and to determine the mechanism of action, with a focus on the peritoneal and intramuscular fat depots. Experimental Design: Obese and STZ-induced diabetic rats were allocated a high fat diet (HFD) and intraperitoneally injected with STZ to mimic an obese and diabetic state. The rats were then orally administered cannabis extract (CE) of 1.25, 2.5 and 5.0 mg/kg body weight (relative to tetrahydrocannabinol (THC) content) or metformin as a positive control. For the obese rat model, the rats were allocated either a high carbohydrate diet (HCD) or high fat diet (HFD) and orally administered with cannabis extract of 1.25 mg/kg body weight (relative to THC content). Weight, blood and insulin-resistant parameters of the rats were monitored. The mitochondrial to genomic DNA ratio (MT:18S DNA), average adipocyte area of the various adipose tissues, citrate synthase and carnitine palmitoyltransferase 1 (CPT1) enzyme activities of the peritoneal and intramuscular fat were measured. Gene expression levels of uncoupling protein 1 (UCP1), cell-death inducing DNA fragmentation factor alpha like effector-a (Cidea), perilipin, hormone-sensitive lipase (HSL) and mitochondrial transcription factor A (TFAM) were measured in peritoneal fat, intramuscular fat and brown adipose tissue (BAT). Main Findings: Obese and STZ-induced diabetic rat model: Due to the biphasic nature of cannabinoids, cannabis dosage plays an important role in the observed effects. CE1.25 was the only cannabis treatment effective in improving the insulinresistant parameters of the rats unlike the other higher cannabis concentrations (CE2.5 and CE5.0). In the peritoneal fat, CE1.25 increased MT:18S DNA, increased citrate synthase activity, and decreased the average adipocyte area when compared to the STZ group. CE1.25 also induced fat beigeing by upregulating gene expression levels of UCP1 and Cidea. XIX Furthermore, an increase in gene expression levels of perilipin, HSL, and TFAM showed increased fat mobilization and metabolic activity. In the intramuscular fat, CE1.25 also reduced the average adipocytes area. However, a different mechanism of action was observed where CE1.25 did not induce fat beigeing, but instead increased both citrate synthase and CPT1 enzyme activities and gene expression levels of HSL, thereby indicating increased fat oxidation and mitochondrial activity.
- Description
- Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2023
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (224 pages)
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
- Rights
- All Rights Reserved
- Rights
- Open Access
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Ramlugon, S (2).pdf | 18 MB | Adobe Acrobat PDF | View Details Download |