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Involvement of adipokines in rimonabant-mediated insulin sensitivity in ob/ob mice
Jogeswar Mohapatra1, Manoranjan Sharma, Satinder Singh
1Zydus Research Centre, Moraiya, Ahmedabad, Gujarat, India.
Objectives:
It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin-sensitising effects of the CB1 antagonist rimonabant is not clear.
Methods:
ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real-time PCR.
Key Findings:
Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor-alpha, visfatin and retinol binding protein-4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated.
Conclusions:
Rimonabant-mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.
Insights
The CB1 antagonist rimonabant improves glucose tolerance and insulin sensitivity in obese mice by altering adipokine expression. Rimonabant downregulates harmful adipokines and upregulates beneficial ones in white adipose tissue.
Area of Science:
- Metabolic research
- Endocrinology
- Pharmacology
Background:
- Type 1 cannabinoid (CB1) receptor blockade shows promise in treating obesity-related metabolic disorders like dyslipidemia, hyperglycemia, and insulin resistance in animal models.
- The specific contribution of adipokines to the insulin-sensitizing effects of CB1 antagonists, such as rimonabant, remains unclear.
Purpose of the Study:
- To investigate the role of adipokines in the insulin-sensitizing effects of the CB1 antagonist rimonabant in obese mice.
- To analyze the impact of rimonabant treatment on the expression of key adipokines in white adipose tissue.
Main Methods:
- Obese (ob/ob) mice were administered varying doses of rimonabant.
- Oral glucose tolerance tests were performed to assess glucose metabolism.
- Quantitative real-time PCR was used to analyze the gene expression of adipokines in white adipose tissue.
Main Results:
- Rimonabant treatment (30 mg/kg) significantly reduced body weight and fat pad weight (P < 0.05) and improved glucose tolerance.
- Gene expression analysis revealed downregulation of tumor necrosis factor-alpha, visfatin, and retinol binding protein-4 in the adipose tissue of rimonabant-treated mice.
- Adiponectin expression was significantly upregulated in response to rimonabant treatment.
Conclusions:
- Alterations in adipokine profiles within white adipose tissue induced by rimonabant may contribute to improved insulin sensitivity in obese animal models.
- These findings highlight a potential mechanism through which CB1 receptor antagonism exerts its metabolic benefits.
