A paper published online with the July 8 issue of Nature delivers a heavy blow to the reputation of one of the prime candidates for a chemical treatment for obesity. Forty-two scientists, from 12 labs, report that they have failed to replicate the effects described in a 2002 study of the gut-derived hormone PYY3-36 on body mass and appetite in rodents.

In 2002, Steve Bloom's lab at London's Imperial College reported that peripheral administration of PYY3-36 reduced appetite and body mass in rats. They followed this up with data showing that it also suppressed appetite in humans over a 24-hour period. The finding that endogenous PYY levels were lower in obese subjects suggested that the peptide plays a causal role in obesity. Furthermore, PYY levels dipped and peaked, respectively, before and after eating—evidence that it regulates appetite on a meal-to-meal basis.

Matthias Tschöp's group at the University of...

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