When researchers first discovered a hormone that suppresses appetite, they must have jumped for joy. Leptin — a safe, naturally occurring hormone — was viewed as a potential breakthrough treatment for obesity, a condition affecting 1.9 billion adults worldwide.
But two decades later, little progress has been made. Leptin, it turns out, does not dampen the desire to eat in overweight individuals because they are resistant to leptin’s appetite-suppressing effects. So much for a fat-fighting wonder drug.
But there is a new ray of hope for a leptin-related obesity treatment. In a new study published in the journal Cell, Boston Children’s Hospital endocrinologist Umut Ozcan and colleagues identified a chemical that appears to make the brain sensitive to leptin.
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Celastrol, a chemical isolated from the root of the thunder god vine reduced food intake by 80 percent in obese mice, compared to untreated obese controls, and led to a 45 percent weight loss, greater than that produced by bariatric surgery in mice.
Thunder god vine, a perennial vine native to Asia, has been used in traditional Chinese medicine for more than 400 years, typically for conditions involving inflammation. Celastrol is present in miniscule amounts in the vine’s roots.
Ozcan’s team previously showed that reducing stress on a cellular component called the endoplasmic reticulum (ER), which moves proteins around a cell, can increase a mouse’s sensitivity to leptin. So they screened a thousand chemicals in search of ones that reduce the hallmarks of ER stress. Celastrol leapt to the top of the heap.
In a series of mouse tests, Celastrol led to dramatic weight loss in obese mice. Additional experiments showed that Celastrol was not toxic in the mice, even when taken long-term, but “mice are not humans,” emphasizes Ozcan, who has applied for a patent for the chemical.
“We urge strong caution for people not to use the root or the extract itself,” he says, as thunder god vine contains numerous other, untested compounds in larger amounts. “Consuming Celastrol or thunder god vine to lose weight could be dangerous.”
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His team hopes to soon initiate human clinical trials to determine the safety of Celastrol as a weight-loss drug.