2014 Mar;142(3):353-60. doi: 10.4067/S0034-98872014000300010.
[A role for the endocannabinoid system in hepatic steatosis].
[Article in Spanish]
Abstract
The endocannabinoid system (ECS) is an important modulator of several metabolic functions. This system is composed by cannabinoid receptors type 1 and 2 (CBR1 and CBR2), their endogenous ligands, known as endocannabinoids, and the enzymes involved in their synthesis and degradation. A deregulated ECS originates metabolic alterations in several tissues, resulting in the typical manifestations of the metabolic syndrome. Liver steatosis of different origins constitutes a physiopathological condition where an altered hepatic ECS is observed. In this condition, there is an increased expression of CBR1 and/or higher endocannabinoid levels in different hepatic cells, which may exert an autocrine/paracrine hyperstimulation of CBR1/CBR2. Activation of CBR1 stimulate the expression of several hepatocyte lipogenic factors, thus leading to increased de novo fatty acids synthesis and consequently to an abnormal accumulation of triglycerides. The effect of CBR2 activity on hepatic function is still controversial because, on one side its stimulation has an interesting protective effect on alcoholic liver disease while, on the other, it may enhance the development of hepatic steatosis in experimental models of diet-induced obesity. In this review we discuss the proposed mechanisms by which ECS is involved in the etiology of hepatic steatosis, as well as the therapeutic possibilities involving peripheral CBR1/CBR2 antagonism/agonism, for the treatment of this condition.
