| dc.description.abstract | The endocannabinoid system (SEC) is an important modulator of several
metabolic functions. This system is composed by cannabinoid receptors type 1
and 2 (RCB1 and RCB2), their endogenous ligands, known as endocannabinoids,
and the enzymes involved in their synthesis and degradation. A deregulated
SEC 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 SEC is observed.
In this condition, there is an increased expression of RCB1 and/or higher
endocannabinoid levels in different hepatic cells, which may exert an autocrine/
paracrine hyperstimulation of RCB1/RCB2. Activation of RCB1 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 RCB2 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 SEC is involved in the etiology
of hepatic steatosis, as well as the therapeutic possibilities involving peripheral
RCB1/RCB2 antagonism/agonism, for the treatment of this condition. | |
