Did you know celastrol and leptin can curb hunger and obesity?

Did you know celastrol and leptin can curb hunger and obesity?
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Celastrol increases the brain’s sensitivity to leptin, the hormone that signals we’ve had enough to eat, but until now, no one knew how this was activated.

Derived from the roots of the thunder god vine, celastrol curbed food intake in obese mice by almost 80%, producing up to a 45% weight loss. Celastrol increases the brain’s sensitivity to leptin, the hormone that signals we’ve had enough to eat, and now published in Nature Medicine, a study led by Umut Ozcan at Boston Children’s Hospital, USA, the mystery of how it curbs hunger and obesity may finally be solved.

Celastrol’s potent anti-obesity effects were previously widely reported

Ozcan’s team initially identified celastrol’s effects several years ago, through a screen of more than 1,000 compounds.

Ozcan later founded ERX Pharmaceuticals to take celastrol and other leptin sensitizers into clinical development; the company is now testing celastrol in Phase 1 clinical trials.

The new study shows that celastrol works through a pro-inflammatory signalling pathway, by boosting amounts of a receptor called IL1R1.

And according to the study, this receptor, which receives signals from the cytokine interleukin 1, is essentially the gatekeeper for celastrol’s metabolic actions.

Ozcan explains: “If you knock out IL1R1, the leptin-sensitizing and anti-obesity effect of celastrol is completely gone.”

Mice deficient in IL1R1 also lost celastrol’s other metabolic benefits, which include curbing insulin resistance/type 2 diabetes.

Inflammation occurs, but is it good?

Scientifically, the finding seems somewhat surprising, but it aligns with Ozcan’s previous discoveries. Papers published in Nature Medicine (2011) and Cell (2017) indicate that the relationship between inflammation and obesity seems to be more complex than previously appreciated. Inflammatory stimuli, cytokines or activation of inflammatory signalling pathways, had been thought to help drive the development of obesity and type 2 diabetes.

However the researchers of this study demonstrated that inflammatory signalling is actually beneficial and needed to keep glucose homeostasis in control. In fact, leptin itself is a pro-inflammatory cytokine.

Avenues that we can still explore

According to the researchers, so far in the early-stage trials, celastrol is demonstrating encouraging weight-loss results and could potentially improve health for the obese, but should it ultimately fail, there may now be other avenues to explore.

“We will now investigate what upregulates IL1R1.” says Ozcan. “It could lead to development of new molecules for the treatment of obesity and associated diseases.

“This is a new chapter for understanding the regulation of hunger.”

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