This paper studied the effects of cannabinoid receptor (CB) 1 antagonism on the regulation of the liver and the adipose tissue lipid metabolism in a mouse model of diet-induced obesity. The experiments were performed on mice previously exposed to a long-term high-sucrose high-fat (HSHF) diet (19 weeks). Results clearly showed that the substantial upregulation of liver CB1 induced by an HSHF diet was fully reversed by the treatment with the CB1 antagonist. The reversion of liver steatosis induced by the treatment with CB1 antagonist was associated with an improvement of adipose tissue metabolism. The authors also reported different degrees of activity of the endocannabinoid system in intra-abdominal (visceral) and subcutaneous fat. For instance, an HSHF diet caused a hyperactivation of lipid metabolism in intra-abdominal adipose tissue that was not observed in subcutaneous fat and CB1 blockade was able to reverse the deleterious effects in intra-abdominal adipose tissue. The improvement of intra-abdominal adipose tissue metabolism appeared to be a determining factor for the normalization of plasma parameters and the reversal of liver steatosis.
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