The Endocannabinoid System as a Target for the Treatment of Visceral Obesity and Metabolic Syndrome

Annals of the New York Academy of Sciences - Tập 1083 Số 1 - Trang 270-305 - 2006
Ioannis Kyrou1, George Valsamakis1, Constantine Tsigos1,2
1Endocrinology, Metabolism and Diabetes Unit, Evgenidion Hospital, Athens University Medical School, Athens 115 28, Greece
2Hellenic National Diabetes Center, Athens 106 75, Greece

Tóm tắt

Abstract:  The endogenous cannabinoid system is a novel, remarkably elaborate physiological signaling system, comprising the recently identified endogenous cannabinoid ligands, their corresponding selective receptors, and the machinery of proteins and enzymes that is involved in their biosynthesis, release, transport, and degradation. This system extends widely in both the central nervous system (CNS) and the periphery and exhibits a variety of actions implicated in vital functions (e.g., behavioral, antinociceptive, neuroprotective, immunosuppressive, cardiovascular, and metabolic). Particular interest has been focused on the apparent participation of endocannabinoids in metabolic homeostasis by modulating the activity of CNS circuits that control food intake and energy expenditure, the neuroendocrine response of the stress system, and the metabolic functions of crucial peripheral tissues, such as the adipose tissue, the gastrointestinal tract, the liver, and the skeletal muscles. These effects are predominantly CB1 receptor mediated and, thus, selective antagonists of this receptor subtype are being vigorously investigated as potential therapeutic agents for the treatment of various metabolic derangements (e.g., obesity, insulin resistance, dyslipidemia, and metabolic syndrome). The first selective CB1 receptor antagonist, rimonabant, has already successfully completed phase III clinical trials as adjunctive obesity treatment, with significant improvements in several associated metabolic and cardiovascular risk factors that led to the recent approval of its clinical use by the Food and Drug Administration.

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Annals of the New York Academy of Sciences

Tập 1083 Số 1

270-305

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