Rola systemu endokanabinoidów w patogenezie i terapii otyłości

• Authors: Maria Pyszniak , Katarzyna Pogoda , Artur Mazur , Jacek Tabarkiewicz

Title variants

EN

The role of Endocannabinoid System in pathogenesis and therapy of obesity

• Languages of publication: PL

Abstracts

PL

Wkrótce po odkryciu pierwszego aktywnego składnika Cannabis sativa -∆ 9 -THC wykazano, iż jego działanie jest zależne od aktywacji specyficznego białka błonowego, tj. receptora kanabinoidowego (CB). Jak dotąd, zidentyfikowano dwa typy tego receptora – CB1 i CB2. Obecnie wiadomo już, że należą one do wewnątrzkomórkowego systemu sygnałowego, nazywanego układem kanabinoidowym (ECS), w którego skład wchodzą także ich ligandy oraz enzymy związane z syntezą i degradacją tych związków. ECS jest obecny w rejonach mózgu związanych z kontrolą odżywiania, a także w tkankach obwodowych odpowiedzialnych za pobór i przetwarzanie energii oraz metabolizm lipidów i glukozy, co wskazuje na udział tego układu w patogenezie otyłości. Liczne badania mówią m.in. o silnym oreksygennym działaniu endokanabinoidów, wywoływanym za pośrednictwem receptorów CB1 w CUN. Co więcej, aktywacja CB1 w tkankach obwodowych nasila lipogenezę, sprzyjając tym samym akumulacji tkanki tłuszczowej w takich narządach, jak wątroba. W trzustce i mięśniach szkieletowych zastosowanie agonistów CB1 indukowało wytworzenie insulinooporności i rozwój hiperglikemii, stanowiących parametry metaboliczne otyłości. Wyniki te dały podstawy do poszukiwania substancji blokujących CB1 o potencjalnej skuteczności w terapii otyłości. Próby przedkliniczne i kliniczne z zastosowaniem rimonabantu – antagonisty/odwrotnego agonisty CB1 – przyniosły korzystne rezultaty w postaci obniżenia masy ciała i zmniejszenia ryzyka powikłań kardiometabolicznych. Jednakże ze względu na poważne psychiatryczne skutki uboczne został on wycofany z obiegu. Celem badań jest przygotowanie leku, który służyłby leczeniu otyłości, jednocześnie nie wywołując powikłań. Ostatnio uwaga naukowców koncentruje się wokół neutralnych antagonistów i selektywnych, odwrotnych agonistów receptorów kanabinoidowych. Endokrynol. Ped. 13/2014;2(47):65-76.

EN

Soon after the discovery of the first active component of Cannabis sativa – -∆ 9 -THC, it has been shown that its action is mediated mainly through the activation of specific membrane protein – cannabinoid receptor (CB). So far two types of this protein were isolated: CB1 and CB2. It is already known that they constitute the intracellular signaling system, called Endocannabinoid System (ECS), which also includes their ligands and enzymes involved in the synthesis and degradation of this compounds. ECS is abundant in the brain regions associated with feeding control and also in peripheral organs regulating food intake and glucose and lipids metabolism, suggesting the crucial role of this system in pathogenesis of obesity. Much evidence has proven potent orexigenic action of endocannabinoids induced via the CB1 receptors activation in CNS. They also stimulate lipogenesis, leading to the fat accumulation in such organs like the liver. Moreover, the CB1 receptor agonist-based treatment induced insulin resistance and development of hyperglycaemia - haracteristic metabolic parameters of obesity. These results has led to the development of CB1-blocking drugs with potential efficacy in obesity treatment. Preclinical and clinical studies with the use fantagonist/inverse agonist – rimonabant have shown significant decrease in body weight and improve in cardiometabolic risk factors. However, serious psychiatric effects of this substance contributed to its withdrawal from the market. The main goal is to design a drug which might prevent obesity without these side effects. Therapies based on the CB1 receptor’s neutral antagonists or selective, inverse agonists might be a promising strategy in obesity treatment. Pediatr. Endocrinol.13/2014;2(47):65-76.

Keywords

EN

Endocannabinoid System; agonist; agonista; antagonist; antagonista; cannabinoid receptor; obesity; otyłość; receptor kanabinoidowy; układ Endokanabinoidowy

Discipline

• MEDICINE: MEDICINE

• Publisher: PROQURAT
• Journal: Endokrynologia Pediatryczna
• Year: 2014
• Volume: 13
• Issue: 2 (47)
• Pages: 65-76

Dates

published

2014

Contributors

author

Maria Pyszniak

author

Katarzyna Pogoda

author

Artur Mazur

author

Jacek Tabarkiewicz

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• Document Type: article