Endocannabinoid system (ECS)

• endocannabinoid system (ECS)
  • neuromodulatory (i.e. influencing the activity of other neurotransmitter systems)
    • has important roles, including the regulation of hormone secretion, and the modulation of immune and inflammatory responses
  • various pathological states, including obesity, are associated with an alteration of endocannabinoid signalling

CB1 and CB2 receptors

• first cannabinoid receptor (CB1) was cloned in 1990, followed, in 1993, by a second receptor (CB2)
  • CB1 receptors are present in high levels in the basal ganglia, cerebellum, hippocampus and cortex express particularly high levels of CB1 receptors
    • the CB1 receptors are also present in other tissues including the peripheral nervous system, the gastrointestinal tract and some blood vessels
  • CB2 receptor expression is mostly restricted to immune tissues and cells.

CB1 and CB2 receptor ligands

• endogenous ligands - these are nown collectively as 'endocannabinoids' and are derived from longchain polyunsaturated fatty acids, in particular, arachidonic
  • the first endocannabinoid, arachidonylethanolamide (anandamide), was isolated from porcine brain in 1992

The endocannabinoid system and obesity

Control of food intake

• ECS acts both peripherally and centrally to control food intake
  • endocannabinoids produced by the gastrointestinal tract appear to modify food consumption by acting on CB1 receptors
  • centrally (in the brain), the ECS drives the motivation to consume highly palatable foods that possess 'high incentive value', which usually means they are fat-dense and calorie-rich (1)
  • short-term food deprivation and/or exposure to palatable foods transiently results in the activation of the ECS in the hypothalamus
    • this increases levels and/or activity of mediators that increase appetite and lipogenesis, whilst also reducing satiation and energy expenditure
  • high-fat diets (which increase the availability of polyunsaturated fatty acid precursors for endocannabinoid biosynthesis) may also lead to ECS hyperactivity

Reference:

1. Br Journ. of Cardiol. 2006; 13:113-120.