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Biological Chemistry

Natural product helps obese mice lose weight

Molecule increases sensitivity to hormone that regulates hunger and energy metabolism

by Michael Torrice
August 8, 2016 | A version of this story appeared in Volume 94, Issue 32

When scientists discovered the hormone leptin in the 1990s, many thought studying its actions would lead to treatments for obesity. Leptin helps regulate hunger, and some scientists have proposed that obesity is the result of resistance to the hormone’s actions.

Now, a team of researchers from Boston Children’s Hospital reports that a natural product can reverse that resistance in obese mice, helping the rodents slim down (Nat. Med. 2016, DOI: 10.1038/nm.4145).

Umut Ozcan and colleagues found this so-called leptin sensitizer by searching through a database that contains cellular gene expression patterns induced by small molecules. The researchers were looking for a molecule that triggered a pattern like that of celastrol, a leptin sensitizer they had discovered previously.

The molecule they found, with­aferin A, reduced weight by 20 to 25% in obese mice fed a high-fat diet. The compound also improved glucose metabolism in the obese mice, suggesting it has antidiabetic effects.

Not only are withaferin A’s effects in mice exciting, says Martin Myers of the University of Michigan Medical School, but so is the method used to find them. By looking for certain gene expression profiles, he says, the method could uncover potential antiobesity molecules that more traditional screens miss.


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