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Isabel Matias "Involvement of the Endocannabinoid System in Obesity"

Abstract :

Endocannabinoids are endogenous lipids produced “on demand”, that bind to and activate the two specific receptors for Cannabis psychoactive principle, Δ9-tetrahydrocannabinol.
Of the two cannabinoid receptor types cloned so far, CB1 receptor is the one most widespread in mammalian tissues, with the highest concentrations in some brain areas, but also present in many other peripheral organs. In particular, CB1 receptors, and endocannabinoids to activate them, have been detected in all the brain and peripheral tissues involved in the control of energy intake, processing and storage, including the hypothalamus, the nucleus accumbens, the vagus nerve and the nodose ganglion, myenteric neurons and epithelial cells of the large intestine, the adipocytes, the pancreas, the skeletal muscle and the liver. Furthermore, CB1 receptors are necessary to induce food intake after food deprivation, to help accumulate fat into adipocytes, to induce lipogenesis in the liver and to reduce energy expenditure. Recent studies indicate that endocannabinoids are produced in response to stressful stimuli such as food deprivation to help re-establishing the homeostasis. CB1 receptor stimulation is short-lasting and limited to those cells or tissues that have been subjected to stress or damage, and it ends once that the organism has recovered from a transient “unbalanced” condition. These physiological responses can be transformed into pathological ones upon repeated consumption of high fat diets, when a permanent hyper-activation of CB1 receptors seems to occur, leading to further food consumption and fat accumulation, and to reduced energy expenditure. Our data indicate that during obesity the endocannabinoid system becomes up-regulated in the adipose tissue and, possibly, in pancreatic β cells, where it might contribute to excessive fat accumulation and insulin release. Adipose tissue and pancreas from mice with diet-induced obesity contain much higher endocannabinoid levels than lean mice. Moreover, patients with obesity or hyperglycaemia caused by type-2 diabetes exhibit higher concentrations of endocannabinoids in visceral fat or serum, respectively. This peripheral hyperactivity of the endocannabinoid system may underlie some of the metabolic consequences of obesity, and allows to predict that CB1 blockers may cause weight loss independent metabolic effects in obese, as opposed to lean, animals and humans. The possible causes and pathological consequences of this phenomenon, and the ways to correct it by using CB1 receptor blockers, will be discussed in this lecture. 

Selected publications

Matias I, Wang JW, Moriello AS, Nieves A, Woodward DF, Di Marzo V.
Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration.
Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):413-8. Epub 2006 Oct 2.
Matias I, Di Marzo V.
Endocannabinoid synthesis and degradation, and their regulation in the framework of energy balance.
J Endocrinol Invest. 2006;29(3 Suppl):15-26. Review.

Giovanni Marsicano