Integrated physiology and pathophysiology of CB1-mediated effects of the endocannabinoid system.

The discovery of the endocannabinoid system (ECS) has raised a large interest in the scientific community providing us with a strikingly long list of apparently independent multi organ effects. As a result, in most reviews on this issue the main function of the ECS is considered as modulatory. Unfortunately, this vision does not add much to our understanding of the specific biological function of the ECS. Thus, modulatory is what in general all biological systems are or should be. In this review we will show that the apparent inconsistent puzzle of the very different tissue specific effects of endocannabinoids (ECs) can be reconstructed in one unitary picture. This picture clearly shows that all the different CB1-mediated effects of ECs sub-serve one major physiological function: to facilitate and increase energy storage. We will also analyze the implications of this unitary vision of the ECS in different contexts. First, in the context of the systems that regulate energy balance, introducing a new systematization based on two homeostatic systems: an endostatic and an exostatic system. Second, in the context of evolution, showing how the function of the ECS has shifted from essential to survival to almost pathological in current times. Finally, in a pathophysiological context, introducing the new concept of "proactive evolution diseases", which can explain the current obesity epidemic and the role the ECS plays in it.