Use of Biopsies of Abdominal Subcutaneous Fat to Study the Role of the Activation of Endocannabinoid 1 Receptors (CB1R) on Adipocyte Glucolipid Metabolism

Overview

Obesity is associated with hyperactivation of the endocannabinoid system, and its inhibition by the administration of CB1 receptor (CB1R) antagonists, leads to a decrease in food intake, weight loss and an improvement in metabolic parameters. Even though the reduction in food intake following central CB1R inactivation seems to be the principal cause of weight loss and the improvement in metabolic parameters, several studies in animals and humans have indicated that peripheral CB1R could also be implicated in the regulation of glucolipid metabolism. As a result, it has been suggested that the long-term beneficial effects of inactivation of the endocannabinoid system are due to both central effects on food intake and peripheral effects involving adipose tissue, the liver, skeletal muscle and the pancreas. It appears essential to determine the role of CB1R located in peripheral tissues and in particular in adipose tissue, which plays an active role in maintaining glucolipid homeostasis. The experiments conducted in this project consist in studying in biopsies of abdominal subcutaneous fat whether activation of adipocyte CB1R modifies adipocyte metabolism by determining the mechanisms. The investigators hypothesize that activation of CB1R in adipose tissue will lead to the stimulation of lipolysis dependent on the alteration of the insulin signal, and therefore that inactivation of the endocannabinoid system by blocking peripheral CB1R could constitute a therapeutic approach to improve obesity-related insulin resistance and dyslipidaemia.

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