Drugs inhibiting cannabinoid receptor type-1 can reduce obesity-associated steatohepatitis

Cannabinoid receptor type 1 antagonist inhibits progression of obesity‐associated nonalcoholic steatohepatitis in a mouse model by remodulating immune system disturbances

In Summary:

Steatohepatitis, a condition often associated with type 2 diabetes and obesity, is the inflammation and accumulation of fat in the liver. Recently, scientists who study the livers of obese mice as a model for this human disease found that these liver tissues exhibited an increase in cannabinoid receptor type 1 (CB1) levels, lipid droplet accumulation and inflammatory responses. The levels of immune cells were also abnormal, with some cell types being too high while others being too low. When the mice received a pharmaceutical compound that blocks the CB1 receptors, these symptoms were reversed.

One of the immune cell types with elevated level in the obese mice’ livers was macrophage. Therefore, follow-up experiments were performed on cells of this type, which showed that concentrated fatty-acids and a selective activator of CB1 induced production of pro-inflammatory molecules by liver macrophage. When the cells were treated with the same pharmaceutical compound that blocks CB1 receptors, such production was again normalized.

The researchers concluded that blockage of CB1 receptors – a member of the endocannabinoid signaling system present in mammals – can correct immune system dysregulations and abnormal inflammation in the liver cells. Although these findings came from mice and cells on Petri dishes, they have great implications on human health: pharmaceutical compounds that inhibit the CB1 receptors can reduce obesity-associated steatohepatitis.


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