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Scientists from the University of Texas Southwestern, USA, may have identified a method of safely mimicking the weight-loss benefits of a plant compound, that despite its harmful side effects hold key answers to developing therapies for obesity.

According to, Celastrol, derived from the root extracts of a white-flowered plant in China, has drawn increased attention in recent years after studies showed it could prevent and reverse obesity in mice.

However, because celastrol could cause reactions such as high blood pressure and lethargy in mice, researchers have sought to understand how the compound works and use that knowledge to develop safe weight-loss treatments for people.

The UT Southwestern researchers may have solved part of the puzzle in a new study that shows celastrol requires a specific protein in a type of neuron that influences metabolism.
The Scientists found that they could mimic a ‘fed’ signal to mouse brains by deleting this protein from the neurons, resulting in mice losing seven per cent of their body weight in two weeks despite being a fed high-fat diet.

The study author, Dr Kevin Williams, an investigator at UT Southwestern’s Center for Hypothalamic Research, said, “This new understanding of how celastrol works on the cellular level opens more possibilities for targeting pathways that can improve our metabolism without the negative health impact.

“We haven’t uncovered all the cell populations that influence weight loss, but each of these findings brings us closer to developing effective, safe therapies for obesity.”

Obesity picture… credit:

The study, which was published in JCI Insight, was the latest research from Williams may someday help improve glucose metabolism in patients with obesity-driven conditions such as diabetes.

The new research focused on a class of cells in the brain called POMC neurons, which are associated with reduced appetite, lower blood glucose levels, and higher energy burning when activated. A 2019 study from Dr. Williams showed a single bout of exercise can boost the activity of POMC for up to two days.
In the latest research, the Williams lab found this neuron also plays a critical part in how celastrol impacts weight loss. Mice given the compound saw decreased activity of a protein called PERK within the region of the brain where POMC neurons reside. The lab further found that deleting PERK from these neurons can replicate much of the weight-loss effects of celastrol, and appears to do so without causing harmful side effects often associated with anti-obesity drugs.

He said, “The mice were leaner and had the same activity levels; they didn’t appear lethargic, sickly or ill. But this is through observation only. Further study is needed to verify how targeting this pathway may be influencing their cardiovascular systems and other functions.”
Data from the World Health Organisation shows that the prevalence of overweight and obesity increased by 20 per cent between 2002 and 2010 in Nigeria.

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