P-V Piazza et al. inNeuron

March 23rd, 2017

The CB1 Receptor as the Cornerstone of Exostasis. Pier Vincenzo Piazza, Daniela Cota, and Giovanni Marsicano. Neuron (2017),Neuron 93, March 22, 2017 ª 2017 Elsevier Inc. 1/j.neuron.2017.02.002/ Volume 93, Issue 6, p1252–1274, 22 March 2017

Giovanni Marsicano DVM, PhD Group Leader Group “Endocannabinoids and Neuroadaptation », Daniela Cota, MD,Group Leader, Group “Energy Balance and Obesity. Pier Vincenzo Piazza, MD, PhD. Team leader: ‘Physiopathology of addiction and traumatic memories’ Neurocentre Magendie

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The discovery and study of the endocannabinoid system (ECS), and in particular its functions mediated by the cannabinoid type-1 receptor (CB1), has helped to write one of the most fascinating chapters in the physiology of multicellular organisms. However, the different physiological roles of CB1-mediated functions still constitute the pieces of a jigsaw puzzle that, taken one by one, give the impression of quite scattered and seemingly unrelated tissue-specific actions.

In this Perspective article on Neuron, Pier-Vincenzo Piazza, Daniela Cota and Giovanni Marsicano try assembling the puzzle of CB1 receptor-dependent effects into a picture that reveals a quite emblematic example of how a biological signaling system, through a variety of coordinated actions in different organs, can regulate exostasis. Endostasis and exostasis are the metabolic and motivational forces able to respond to the main problem of living beings that is the subtraction of energy from the external world, its accumulation and its consumption. Whereas endostasis responds to the immediate needs of the body, exostasis evolved to fulfill future needs through the accumulation of energy reserves.  The authors propose that the actions of CB1 receptors in the brain and the body represent a prototypical exostatic system.
First, they provide a short description of the biological organization of the ECS including its molecular components, body distribution and signaling pathways.
Second, they discuss how exostatic facilitation of energy storage has been necessary for the survival of species during evolution, although this function seems nowadays a gateway to pathology. Third, they integrate different functions of CB1 receptors and provide evidence that they perfectly serve exostatic processes to promote energy storage.

Finally, they introduce the concept of proactive evolution-induced diseases (PEID), which can explain the seemingly paradoxical nature of how an evolutionarily selected physiological function can become the cause of an epidemic pathological condition such as obesity.

Giovanni Marsicano DVM, PhD Group Leader NeuroCentre Magendie U1215 INSERM Université Bordeaux Group “Endocannabinoids and Neuroadaptation”