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
- Authors: Ramlugon, Sonaal
- Date: 2023-04
- Subjects: Rats as laboratory animals , Diabetes in practice , Cannabis -- South Africa
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10948/61282 , 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. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2023
- Full Text:
- Date Issued: 2023-04
- Authors: Ramlugon, Sonaal
- Date: 2023-04
- Subjects: Rats as laboratory animals , Diabetes in practice , Cannabis -- South Africa
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10948/61282 , 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. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2023
- Full Text:
- Date Issued: 2023-04
The effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells
- Authors: Ramlugon, Sonaal
- Date: 2014
- Subjects: Cannabinoids , Adipose tissues , Cannabis -- Therapeutic use
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10361 , http://hdl.handle.net/10948/d1021072
- Description: During the 1800’s cannabis use was described as a treatment for a variety of metabolic disorders but its recreational use in the twentieth century resulted in laws which made the usage of cannabis illegal despite its medicinal properties. Cannabis usage has been reported to be useful in the treatment of Type 2 diabetes but unfortunately conflicting results are often published and its mechanism of action is still unknown. The aim of this project was to investigate the effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells, to unravel their mechanism of action and also to test for potential anti-diabetic properties. The studies showed that phytocannabinoid treatment promoted higher glucose uptake and significantly less fat accumulation when compared to Rosiglitazone. Rosiglitazone is an anti-diabetic drug that has recently been withdrawn from the market since its usage has been associated with severe side effects. It was also found that during the 1800’s cannabis use was described as a treatment for a variety of metabolic disorders but its recreational use in the twentieth century resulted in laws which made the usage of cannabis illegal despite its medicinal properties. Cannabis usage has been reported to be useful in the treatment of Type 2 diabetes but unfortunately conflicting results are often published and its mechanism of action is still unknown. The aim of this project was to investigate the effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells, to unravel their mechanism of action and also to test for potential anti-diabetic properties. The studies showed that phytocannabinoid treatment promoted higher glucose uptake and significantly less fat accumulation when compared to Rosiglitazone. Rosiglitazone is an anti-diabetic drug that has recently been withdrawn from the market since its usage has been associated with severe side effects. It was also found that phytocannabinoid treatment was able to reverse the insulin-resistant state of 3T3-L1 cells. The study indicates that the mechanism of action occurs at the mitochondrial level where enzymes such as succinate dehydrogenase and glycerol-3-phosphate dehydrogenase are modulated thereby affecting oxidative phosphorylation involved in the respiratory chain. In addition the effect observed with phytocannabinoid treatment is time dependent and affects the cells differently at different developmental stages. Therefore it can be concluded that phytocannabinoid treatment not only helps to maintain the balance between adipogenesis and lipolysis in 3T3-L1 cells but its use may also be helpful in the treatment of Type 2 diabetes and/or obesity-related insulin resistance.phytocannabinoid treatment was able to reverse the insulin-resistant state of 3T3-L1 cells. The study indicates that the mechanism of action occurs at the mitochondrial level where enzymes such as succinate dehydrogenase and glycerol-3-phosphate dehydrogenase are modulated thereby affecting oxidative phosphorylation involved in the respiratory chain. In addition the effect observed with phytocannabinoid treatment is time dependent and affects the cells differently at different developmental stages. Therefore it can be concluded that phytocannabinoid treatment not only helps to maintain the balance between adipogenesis and lipolysis in 3T3-L1 cells but its use may also be helpful in the treatment of Type 2 diabetes and/or obesity-related insulin resistance.
- Full Text:
- Date Issued: 2014
- Authors: Ramlugon, Sonaal
- Date: 2014
- Subjects: Cannabinoids , Adipose tissues , Cannabis -- Therapeutic use
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10361 , http://hdl.handle.net/10948/d1021072
- Description: During the 1800’s cannabis use was described as a treatment for a variety of metabolic disorders but its recreational use in the twentieth century resulted in laws which made the usage of cannabis illegal despite its medicinal properties. Cannabis usage has been reported to be useful in the treatment of Type 2 diabetes but unfortunately conflicting results are often published and its mechanism of action is still unknown. The aim of this project was to investigate the effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells, to unravel their mechanism of action and also to test for potential anti-diabetic properties. The studies showed that phytocannabinoid treatment promoted higher glucose uptake and significantly less fat accumulation when compared to Rosiglitazone. Rosiglitazone is an anti-diabetic drug that has recently been withdrawn from the market since its usage has been associated with severe side effects. It was also found that during the 1800’s cannabis use was described as a treatment for a variety of metabolic disorders but its recreational use in the twentieth century resulted in laws which made the usage of cannabis illegal despite its medicinal properties. Cannabis usage has been reported to be useful in the treatment of Type 2 diabetes but unfortunately conflicting results are often published and its mechanism of action is still unknown. The aim of this project was to investigate the effect of phytocannabinoid treatment on adipogenesis and lipolysis in 3T3-L1 cells, to unravel their mechanism of action and also to test for potential anti-diabetic properties. The studies showed that phytocannabinoid treatment promoted higher glucose uptake and significantly less fat accumulation when compared to Rosiglitazone. Rosiglitazone is an anti-diabetic drug that has recently been withdrawn from the market since its usage has been associated with severe side effects. It was also found that phytocannabinoid treatment was able to reverse the insulin-resistant state of 3T3-L1 cells. The study indicates that the mechanism of action occurs at the mitochondrial level where enzymes such as succinate dehydrogenase and glycerol-3-phosphate dehydrogenase are modulated thereby affecting oxidative phosphorylation involved in the respiratory chain. In addition the effect observed with phytocannabinoid treatment is time dependent and affects the cells differently at different developmental stages. Therefore it can be concluded that phytocannabinoid treatment not only helps to maintain the balance between adipogenesis and lipolysis in 3T3-L1 cells but its use may also be helpful in the treatment of Type 2 diabetes and/or obesity-related insulin resistance.phytocannabinoid treatment was able to reverse the insulin-resistant state of 3T3-L1 cells. The study indicates that the mechanism of action occurs at the mitochondrial level where enzymes such as succinate dehydrogenase and glycerol-3-phosphate dehydrogenase are modulated thereby affecting oxidative phosphorylation involved in the respiratory chain. In addition the effect observed with phytocannabinoid treatment is time dependent and affects the cells differently at different developmental stages. Therefore it can be concluded that phytocannabinoid treatment not only helps to maintain the balance between adipogenesis and lipolysis in 3T3-L1 cells but its use may also be helpful in the treatment of Type 2 diabetes and/or obesity-related insulin resistance.
- Full Text:
- Date Issued: 2014
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