Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipokines / blood
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Adipokines / deficiency
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Adipokines / physiology*
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Adiponectin / blood
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Adipose Tissue / drug effects
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Adipose Tissue, White / drug effects*
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Adipose Tissue, White / metabolism
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Animals
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Anti-Obesity Agents / pharmacology
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Anti-Obesity Agents / therapeutic use*
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Blood Glucose / metabolism
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Body Weight / drug effects
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Down-Regulation
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Female
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Gene Expression
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Glucose Intolerance / drug therapy*
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Glucose Intolerance / metabolism
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Glucose Tolerance Test
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Insulin / blood
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Insulin Resistance*
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Leptin / deficiency
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Mice
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Mice, Knockout
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Models, Animal
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Nicotinamide Phosphoribosyltransferase / genetics
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Nicotinamide Phosphoribosyltransferase / metabolism
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Obesity / drug therapy*
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Organ Size / drug effects
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Piperidines / pharmacology
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Piperidines / therapeutic use*
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Pyrazoles / pharmacology
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Pyrazoles / therapeutic use*
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RNA, Messenger / metabolism
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Retinol-Binding Proteins, Plasma / genetics
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Retinol-Binding Proteins, Plasma / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Rimonabant
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Adipokines
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Adiponectin
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Anti-Obesity Agents
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Blood Glucose
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Insulin
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Leptin
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Piperidines
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Pyrazoles
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RNA, Messenger
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Rbp4 protein, mouse
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Receptor, Cannabinoid, CB1
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Retinol-Binding Proteins, Plasma
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Tumor Necrosis Factor-alpha
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Nicotinamide Phosphoribosyltransferase
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Rimonabant