The endocannabinoid system as a link between homoeostatic and hedonic pathways involved in energy balance regulation.

Excessive consumption of high energy, palatable food contributes to obesity, which results in the metabolic syndrome, heart disease, type-2 diabetes and death. Current knowledge on the function of the hypothalamus as the brain "feeding center" recognizes this region as the main regulator of body weight in the central nervous system. Because of their intrinsically fast and adaptive activities, feeding-controlling neural circuitries are endowed with synaptic plasticity modulated by neurotransmitters and hormones that act at different hierarchical levels of integration. In the hypothalamus, among the chemical mediators involved in this integration, endocannabinoids are ideal candidates for the fast (i.e., non-genomic), stress-related fine-tuning of neuronal functions. In this article, we overview the role of the endocannabinoid system in the control of energy intake, and particular in the consumption of high energy, palatable food, and discuss how such role is affected in the brain by changes in the levels of feeding-regulated hormones, such the adipose tissue-derived anorexigenic mediator leptin, as well as by high fat diets. The understanding of the molecular mechanisms underlying the neuronal control of feeding behaviors by endocannabinoids offers many potential opportunities for novel therapeutic approaches against obesity. Highlights of the latest advances in the development of strategies that minimize central endocannabinoid overactivity in "western diet"-driven obesity are discussed.