Cannabinoid Receptor 2 Could be Antiobesity Target

Italian researchers have found that the cannabinoid receptor 2 (CB2) could be a pharmacological target for treating or preventing obesity, according to a study recently published in The Journal of Clinical Endocrinology & Metabolism.

The researchers, led by Francesca Rossi, MD, of the Second University of Naples, point out that obesity is associated with low-grade inflammation and adipocyte (ADP) hyperplasia/hypertrophy, and also inhibits browning of adipose tissue. They also note that CB2 agonists have been shown to reduce food intake in mice. The investigators also wanted to look at a common CB2 variant, Q63R, which can reduce CB2 function and has been linked to eating disorders.

“these data suggest CB2 receptor may be a novel target for inducing browning, possibly through up-regulation of IL-4 and induction of [uncoupling protein] UCP-1 signaling.”

Rossi and her team evaluated the effects of the CB2 receptor as it relates to childhood obesity by analyzing the CB2-Q63R variant in 501 obese Italian children who were referred to the Department of Women, Children and General and Specialized Surgery of the Second University of Naples from January 2010 to August 2014. They also wanted to see the effects of CB2 agonist JWH-133 and the reverse agonist AM630 had on ADP activity and morphology, so they “performed molecular, biochemical, and morphological studies on in vitro ADPs, differentiated from mesenchymal stem cells (MSCs) of healthy adult donors or derived from sc adipose tissue of nonobese and obese adult subjects,” the authors write.

They found that the CB2 variant Q63R was significantly associated with a high BMI score and the reverse CB2 agonist AM630 increased inflammatory effects, fat storage, and reduced adipose browning. “CB2 agonist JWH-133 reversed all of the obesity-related effects,” they write.

Based on these results, the researchers conclude that the CB2 receptor could be a target for reducing obesity. Since the researchers also conducted a MRNA analysis, they were able to see which genes were affected as well. They write that “these data suggest CB2 receptor may be a novel target for inducing browning, possibly through up-regulation of IL-4 and induction of [uncoupling protein] UCP-1 signaling.”

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